Hsp90 Interactors

Total Page:16

File Type:pdf, Size:1020Kb

Hsp90 Interactors Picard, 09/2021 - Page 1 HSP90 INTERACTORS Chaperones and relatives - valosin-containing protein - MAFG (VCP)/p97 - Mal63 - MalR - Aha1 and its homolog Hch1 - USP19 - MAX - Cdc37 (p50) and its relative - Tsc1 - Met1 Harc (= Cdc37L1) - ZMYND10 - MeSRS1 - p23 (=Sba1) - GIGANTEA - MeWRKY20 - proteins with TPR motifs: - Ids2 - MKX Hop (=Sti1), FKBP52 - TIMP2 - mod(mdg4) (=FKBP4; and high MW - Cereblon - c-Myc plant homologs), FKBP51 - Nanog (=FKBP5), FKBP8 Transcription factors - NFIC (=FKBP38), FKBP36 (= - NFRKB FKBP6), Plasmodium - Notch1 (ICN1) FKBP35, plant TWD1, - 12(S)-HETE receptor - NR1H3 cyclophilin-40 (Cpr6 and - AF9/MLLT3 - NR1I2 Cpr7), PP5 (and yeast Ppt1), - all vertebrate steroid - Oct4 Tom70, probably also receptors (GR, MR, ERa, - p53 related Tom71=Tom72, XAP- ERb, PR, AR) - p73 2 (=AIP=ARA9), Cns1 and its - AGL24 - PAS family members: Drosophila and human - ATF3 Dioxin receptor (=AhR), Sim, relatives Dpit47 and TTC4, - BBX HIF–1a, HIF-2a, HIF-3a CHIP, UNC45A (GC-UNC45) - BCL-6 - PCGF6 and UNC45B, She4, DnaJC7 - Bclaf1 - POGK (=Tpr2=mDj11=CCRP), CRN, - BES1 - PPARa, PPARb, PPARγ, WISp39 (=FKBPL), Tah1 - BrZ7 PPARδ (=Spaghetti=RPAP3), Spag1, - BZR1 - PRDM1 NASP, Toc64 and OM64, - C20orf194 - PREB TPR1 (=Ttc1), SGT - CAR - PXR (=aSGT=SGTA), DYX1C1, - C/EBPb - REST AtTPR1, AtTPR2, AtTPR7, - CEBPE (C/EBPε) - REV-ERBa AIPL1, Tom34, Tetrahymena - Cwt1 - RlmA (of Aspergillus) Coi12p - CXXC1 - SETDB1 - CS-containing p23 relatives - cytoplasmic v-erbA - SIM2 AARSD1, SGT1 (=SUGT1), - DLX6 - SLFN11 RAR1, Siah-1-interacting - DMRTA1 - SOC1 protein (SIP), - E1A - SOX11 Chp1/CHORDC1/Morgana, - E2F1 and E2F2 - Sp1 B-ind1, melusin, NudC and - EcR - SREBF1 NudCL2 (=Nudcd2) - FOXD4L6 - SREBP1 - FNIP1, FNIP2 - FOXM1 - SREBP2 - Hsc70/Hsp70/Hsp72/DnaK - FOXP2 - Stat2 - Hsp60 - GTF2IRD2 - Stat3 (also in caveolin-1 - mtHsp70/Grp75/mortalin - Hap1 complexes in rafts) - Human DnaJ homolog - HCFC1 - Stat5 Hsj1b, cynobacterial DnaJ2 - HMGA1, HMGA2 - SUP - PhLP2A - HNF4A - TADA2A - Pih1 (=Nop17) (mostly - HP1BP3 - TBX22 through Tah1) - HSF-1 - TCF25 - Prefoldin 4 and 6 - HsfA1, HsfA2, HsfB1 - TDP-43 - S100A1 - IRF2 - TEAD2 - Sse1, Sse2 - IRF3 - TFDP3 - Tel2-Tti1-Tti2 complex - ISX - THAP4 - Toxoplasma Sis1-like - LFY - TonEBP/OREBP Picard, 09/2021 - Page 2 - TRIM32 - CDK11B - HIPK4 - Tup1 - CDK14 - HopBF1 effectors - Twist1 - CDK15 - ICK - Ure2 - CDK18 - INSRR - USP1 - Cdk2, Cdk4, Cdk6, Cdk9, - Insulin receptor - VDR Cdk11 - Insulin-like growth factor 1 - VP16 - CDK3 receptor - water mold Achlya steroid - CheA (E. coli) - Integrin-linked kinase (antheridiol) receptor - Chk1 - IP6K2 - WT1 - Cla4 - IRAK-1 - ZBED4 - CLK2 - IRAK2 - ZBTB17 - CLK3 - IRAK3 - ZBTB20 - Cot = Tpl-2 - Ire1a - ZC3H7B - CSF1R - ITK - ZNF215 - CSNK1A1 - IkB kinases (IKK) a, b, g, e - ZNF509 - DCLK2 - JAK1 - ZNF74 - DDR1 - JNK - DDR2 - KSR Kinases - Death-associated kinases - LATS1, LATS2 DAPK, DAPK2, DAPK3 - LCK - DLK - LIMK1 - ACVR1B - DMPK - LIMK2 - ACVR1C - DYRK1B - Lkb1 - ACVR2B - DYRK2 - LMTK3 - Akt/PKB - DYRK3 - LRRK2 - AKT2 - DYRK4 - LYN - ALK - eEF-2 kinase - MAP2K5 - ALK1, ALK5 - EGF receptor (mutant and - MAP2K7 - ALPK1 wt) - MAP3K12 - AMHR2 - eIF2-a kinases HRI, Gcn2, - MAP3K15 - AMPKa, AMPKg Perk, PKR - MAP3K2 - ARAF - Eml4-Alk - MAP3K6 - ASK1 - EPHA1 - MAP3K9 - ATM - EphA2 - MAP4K1 - AURKC - EPHA4 - MAP4K2 - Aurora B - EPHB1 - MAP4K4 - AXL - EPHB6 - MAPKKK (MEKK) YODA - Bcr-Abl - ErbB2 - MAPK15 - BCR-FGFR1 - ERBB3 - MAPK4 - BGLF4 of EBV - ERBB4 - MAPK6 - BLK - ERK5 - MAPK7 - BMPR1A - FASTK - MAST1 - BMX - FGFR1 - MAST2 - BTK - FGFR3 and FGFR4 - MATK - c-Abl - Flt3 - MEK - c-Kit - FLT4 - MEKK1 and MEKK3 - c-Mos - FOP2-FGFR1 - MERTK - CAMK1G - FRK - MET - CAMK2A - Fused - Mik1 - CAMK2B - FYN - MINK1 - CAMK2D - Gal1 - MLK3 - CAMK2G - GRK2 and GRK6 - MLKL - CAMK4 - GRK4 - MOK, MAK, MRK - CAMKK1 - GRK7 - MpkA (of Aspergillus) - CAMKK2 - GSK3A - Mps1 - CAMKV - GSK3b - mTOR - casein kinase IIa catalytic - HCK - MUSK subunit - HER3 - MYLK2 - Cdc2 (=Cdk1) - HIPK2 - MYLK3 Picard, 09/2021 - Page 3 - MYLK4 - RET Others - NEK11 - RET/PTC1 - NEK8 - RIP1 - NEK9 - RIP3 - Act1 (=TRAF3IP2) - NIK - Ron - Adenosine A2A receptor - NPM-Alk - ROR1 - a2C adrenergic receptor - NPR2 - ROR2 - Ago3 - NTRK1 - RPS6KA1 - AID - NTRK2 - RPS6KA2 - AIP56 - NTRK3 - RPS6KA3 - Aldo-keto reductase 1B10 - NUAK2 - RPS6KA5 - ANAPC2 - Nucleophosmin-Anaplastic - RPS6KA6 - ANKMY2 Lymphoma Kinase - RPS6KB1 - Annexin A2 - p38 - RPS6KC1 - ANP receptor - p90RSK - RPS6KL1 - ANP32C/D - PAK6 - Ryk - Apaf-1 - PASK - SGK-1 - APH1 - Pbs2 - SGK2 - apoB - PDGFRB - SGK223 - APOBEC-3B, -3C, -3G - PDIK1L - SGK3 - Arb1 - PDK1 - Slt2 - ARD1 - PGK1 - src related tyrosine kinases: - Argonaute-1 (Ago1) - PI4KIIb fer, fes, fgr, fps, lck, yes - Argonaute-2 (=Ago2=GERp95) - Pim-1 - SRPK1 - Argonaute-4 (Ago4) - PIM2 - SRPK3 - ARMC5 - PIM3 - SSCMK1 - ArtAB - Pink1 - STK32B - ASB17 - PKCl, PKCe and other PKCs - STK32C - ASB2 - PKM2 - STK33 - ASB3 - PKN1 - STK38 - ASB4 - PKN2 - STK38L - ASB6 - platelet-derived growth - STYK1 - ASL factor receptor a - SYK - ASS1 - Plk1 - TAK1 - ATG8 (GABARAP) proteins - Plk3 - TAOK3 - ATG8b, ATG8c, ATG8e, - Pnck - TBK1 ATG12 - pp60v-src, c-src - TESK1 - Axin 1 - PRKAA2 - TESK2 - BCAP (PIK3AP1) - PRKACB - TGFb receptors I and II - BALF5 of EBV - PRKCA - TIE1 - Bcl-2 - PRKCB - TNK1 - Bcl-xL - PRKCG - TNK2 - Beclin 1 - PRKCH - TNNI3K - Bid - PRKCI - TP53RK - BIN2 - PRKCQ - TrkAI and III - BLM helicase - PRKCZ - TrkB - Bms1 - PRKD1 - TSSK1B - BPIFB4 - PRKD2 - TSSK2 - BRAT1 - PRKDC - TSSK3 - BRCA1 - PRKG2 - TSSK4 - BRCA2 - PRKX - TSSK6 - BRD4 - PRKY - Tyk2 - BRMS1 - PSKH1 - TYRO3 - BTRC - PSKH2 - Ulk1 - c-IAP1 - PTK2 - VEGFR1, VEGFR2 - calcineurin (Cna2; catalytic - PTK2B - Wee1, Swe1 subunit) - PTK6 - WNK4 - calmodulin - PTK6 - ZAP-70 - calmodulin - Raf-1, B-Raf, Ste11 methyltransferase Picard, 09/2021 - Page 4 - calpain-1 - DNA polymerase λ - glutathione S-transferase - calponin - DNA polymerase h subunit 3 (KS type) - CARM1 - DnaA (E. coli) - Guanylate cyclase, soluble - Caspase-8 - DNMT1 - Ga0, Ga12 - b-catenin - Dsn1 - Glucocerebrosidase - CB2 cannabinoid receptor - DTX4 - GREB1 - Ccp1 - E6^E7 - HAX-1 - CCDC117 - EBAX-1 - HDAC1 - CD38 type III - Emc2 - HDAC6 - CD79a - ENC1 - HECTD3 - Cdc13 - eNOS, nNOS (?) - Hepatitis B virus core - Cdc14 - ether-a-gogo-related protein - Cdc25a and Cdc25c potassium channel (ERG = - Hepatitis C virus protein - Cdk5 activator p35 HERG = KCNH2) NS3 - CPEB1, CPEB2, CPEB3 - EZH2 - Hepatitis E virus capsid - CFTR (nascent and mutant - F1F0-ATP synthase protein polypeptide) - FANCA - HERC4 - ChAT - FBXL12 - HERC6 - CheZ (E. coli) - FBXL13 - Histones H1, H2A, H2B, H3 - Chl1 - FBXL14 and H4 - Chronophin - FBXL15 - HMGCR - Cineole synthase 1 - FBXL18 - Hsp27 - Clathrin heavy chain - FBXL2 - Humanin - CLC-1 chloride channel - FBXL3 - Huntingtin - CLC-2 chloride channel - FBXL6 - IDH1 - Clostridium toxin CDT - FBXL8 - Importin 4 (IPO4) - Clostridium toxin iota - FBXO10 - Importin b1 - Clusterin - FBXO17 - Importin-a6 (KPNA5) - COG complex - FBXO18 - Ino80 - COI1 - FBXO24 - Inositol 1,4,5-trisphosphate - Complement C9 - FBXO25 receptor 3 - Cry toxins - FBXO27 - Integrin a2 - CTA1 = CtxA1 - FBXO28 - Integrin a4 - Ctf13/Skp1 component of - FBXO3 - Integrin aL CBF3 - FBXO34 - IL-1b - CUL1 - FBXO38 - IRS-2 - CUL2 - FBXO4 - Japanese encephalitis virus - CUL3 - FBXO40 E protein - CUL4A - FBXO6 - JlpA - CUL4B - FBXO9 - KAP1 - Cup - FBXW11 - KAT5 - cyclin B - FBXW2 - KBTBD4 - cyclophilin D - FBXW5 - KBTBD7 (mitochondrial) - FBXW7 - KCNA5 - Cyr1 - FGAMS - KCNA6 - cytoskelettal proteins: - Fibronectin - KCNG1 actin, tubulin (including - Filamin A - KCNS3 ciliary b4-tubulin), myosin - FliN, FliI (E. coli) - KCNQ4 (including Myo3B) - FLIPS and FLIPL - KCTD8 - DBC2 - Folliculin - KDM3A/JMJD1A - DDX5 - free bg subunit of G protein - KDM4B/JMJD2B - DEDD - FtsZ - KEAP1 - Dengue virus protein E - G2E3 - KIAA0317 - Dengue virus proteins - GAN - Kir6.2 NS1/2B/3/4B/5 - GBP1 - KLHL1 - DET1 - Gln1 - KLHL10 - Diphtheria toxin A - GLT-1 - KLHL13 - DNA helicase Ssl2 - GluR1 - KLHL14 - DNA polymerase a - KLHL15 Picard, 09/2021 - Page 5 - KLHL22 - MUC1 - PLCg - KLHL23 - Myoglobin - PLN - KLHL25 - N-myc downstream- - polysomal ribonuclease 1 - KLHL26 regulated gene 1 (NRDG1) (PMR1) - KLHL29 - N-WASP - PPAT - KLHL32 - Na+-K+-Cl- cotransporter 1 - PRDM14 - KLHL34 - NadA - PRMT5 - KLHL36 - NAP1 - pro-Dcp1 - KLHL38 - NB-LRR proteins: RPM1 and - prolactin receptor - KLHL6 RPS2, Nod1, Nod2, NALP2, - prostacyclin synthase - knob complexes (in the NALP3, NALP4, NALP12, - proteasome membrane of Plasmodium- IPAF, RPP4 - PRPF8 infected erythrocytes) - NBR1 - PRPF19 - KSHV K1 - NCC - PTPN22 - KSR1 - NCT - Ptx - KSR2 - NDRG2 - PUS7 - L protein of HRSV - NELF-E - R-protein I-2 - L protein of SHVV - Nervous necrosis virus - R2TP complex through Pih1 - Lamin A/C capsid protein - Rab-aGDI - LAMP-2A - Neuraminidase - Rab3a - LANA of KS-HSV - Neuropeptide Y - Rab11a - LAP - NHE1 - RAB40A - LARP4B - NHLRC1 - Rac/Rop GTPase Rac1 (rice) - Legumain - Nibrin - Rac1 - LGALS3BP - NleH1 and NleH2 - Rad51 - LIS1 - NMNAT2 - Rad52 - LNX1 - Norovirus capsid protein - RAG1 - LOC440248 VP1 - Ral-binding protein 1 - LOX1 (OLR1) - Nox1, Nox2, Nox3, Nox5 (RalBP1) - LOXL2 - NS1 - RanBP9 - Lpl1 (S. aureus) - Nsl1 - Rapsyn - LRP1 (=CD91) - nsP3 and nsP4 of - Raptor - LRP5 Chikungunya virus - RCBTB1 - LRSAM1 - Nucleoprotein (NP) of - RCBTB2 - LSD1 MERS-CoV - RCP - LSM8 - Nup62 - Reovirus protein s1 - macromolecular aminoacyl- - Nwd1 - REV1 tRNA synthetase complex - OGT - reverse transcriptase of - Macrophage scavenger - OsCERK1 hepatitis
Recommended publications
  • Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes
    G C A T T A C G G C A T genes Article Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes Filip Pajpach , Linda Shearwin-Whyatt and Frank Grützner * School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; fi[email protected] (F.P.); [email protected] (L.S.-W.) * Correspondence: [email protected] Abstract: Chromosome segregation at mitosis and meiosis is a highly dynamic and tightly regulated process that involves a large number of components. Due to the fundamental nature of chromosome segregation, many genes involved in this process are evolutionarily highly conserved, but duplica- tions and functional diversification has occurred in various lineages. In order to better understand the evolution of genes involved in chromosome segregation in mammals, we analyzed some of the key components in the basal mammalian lineage of egg-laying mammals. The chromosome passenger complex is a multiprotein complex central to chromosome segregation during both mitosis and meio- sis. It consists of survivin, borealin, inner centromere protein, and Aurora kinase B or C. We confirm the absence of Aurora kinase C in marsupials and show its absence in both platypus and echidna, which supports the current model of the evolution of Aurora kinases. High expression of AURKBC, an ancestor of AURKB and AURKC present in monotremes, suggests that this gene is performing all necessary meiotic functions in monotremes. Other genes of the chromosome passenger complex complex are present and conserved in monotremes, suggesting that their function has been preserved Citation: Pajpach, F.; in mammals.
    [Show full text]
  • Supplementary Information Material and Methods
    MCT-11-0474 BKM120: a potent and specific pan-PI3K inhibitor Supplementary Information Material and methods Chemicals The EGFR inhibitor NVP-AEE788 (Novartis), the Jak inhibitor I (Merck Calbiochem, #420099) and anisomycin (Alomone labs, # A-520) were prepared as 50 mM stock solutions in 100% DMSO. Doxorubicin (Adriablastin, Pfizer), EGF (Sigma Ref: E9644), PDGF (Sigma, Ref: P4306) and IL-4 (Sigma, Ref: I-4269) stock solutions were prepared as recommended by the manufacturer. For in vivo administration: Temodal (20 mg Temozolomide capsules, Essex Chemie AG, Luzern) was dissolved in 4 mL KZI/glucose (20/80, vol/vol); Taxotere was bought as 40 mg/mL solution (Sanofi Aventis, France), and prepared in KZI/glucose. Antibodies The primary antibodies used were as follows: anti-S473P-Akt (#9271), anti-T308P-Akt (#9276,), anti-S9P-GSK3β (#9336), anti-T389P-p70S6K (#9205), anti-YP/TP-Erk1/2 (#9101), anti-YP/TP-p38 (#9215), anti-YP/TP-JNK1/2 (#9101), anti-Y751P-PDGFR (#3161), anti- p21Cip1/Waf1 (#2946), anti-p27Kip1 (#2552) and anti-Ser15-p53 (#9284) antibodies were from Cell Signaling Technologies; anti-Akt (#05-591), anti-T32P-FKHRL1 (#06-952) and anti- PDGFR (#06-495) antibodies were from Upstate; anti-IGF-1R (#SC-713) and anti-EGFR (#SC-03) antibodies were from Santa Cruz; anti-GSK3α/β (#44610), anti-Y641P-Stat6 (#611566), anti-S1981P-ATM (#200-301), anti-T2609 DNA-PKcs (#GTX24194) and anti- 1 MCT-11-0474 BKM120: a potent and specific pan-PI3K inhibitor Y1316P-IGF-1R were from Bio-Source International, Becton-Dickinson, Rockland, GenTex and internal production, respectively. The 4G10 antibody was from Millipore (#05-321MG).
    [Show full text]
  • Kinase Profiling Book
    Custom and Pre-Selected Kinase Prof iling to f it your Budget and Needs! As of July 1, 2021 19.8653 mm 128 196 12 Tyrosine Serine/Threonine Lipid Kinases Kinases Kinases Carna Biosciences, Inc. 2007 Carna Biosciences, Inc. Profiling Assays available from Carna Biosciences, Inc. As of July 1, 2021 Page Kinase Name Assay Platform Page Kinase Name Assay Platform 4 ABL(ABL1) MSA 21 EGFR[T790M/C797S/L858R] MSA 4 ABL(ABL1)[E255K] MSA 21 EGFR[T790M/L858R] MSA 4 ABL(ABL1)[T315I] MSA 21 EPHA1 MSA 4 ACK(TNK2) MSA 21 EPHA2 MSA 4 AKT1 MSA 21 EPHA3 MSA 5 AKT2 MSA 22 EPHA4 MSA 5 AKT3 MSA 22 EPHA5 MSA 5 ALK MSA 22 EPHA6 MSA 5 ALK[C1156Y] MSA 22 EPHA7 MSA 5 ALK[F1174L] MSA 22 EPHA8 MSA 6 ALK[G1202R] MSA 23 EPHB1 MSA 6 ALK[G1269A] MSA 23 EPHB2 MSA 6 ALK[L1196M] MSA 23 EPHB3 MSA 6 ALK[R1275Q] MSA 23 EPHB4 MSA 6 ALK[T1151_L1152insT] MSA 23 Erk1(MAPK3) MSA 7 EML4-ALK MSA 24 Erk2(MAPK1) MSA 7 NPM1-ALK MSA 24 Erk5(MAPK7) MSA 7 AMPKα1/β1/γ1(PRKAA1/B1/G1) MSA 24 FAK(PTK2) MSA 7 AMPKα2/β1/γ1(PRKAA2/B1/G1) MSA 24 FER MSA 7 ARG(ABL2) MSA 24 FES MSA 8 AurA(AURKA) MSA 25 FGFR1 MSA 8 AurA(AURKA)/TPX2 MSA 25 FGFR1[V561M] MSA 8 AurB(AURKB)/INCENP MSA 25 FGFR2 MSA 8 AurC(AURKC) MSA 25 FGFR2[V564I] MSA 8 AXL MSA 25 FGFR3 MSA 9 BLK MSA 26 FGFR3[K650E] MSA 9 BMX MSA 26 FGFR3[K650M] MSA 9 BRK(PTK6) MSA 26 FGFR3[V555L] MSA 9 BRSK1 MSA 26 FGFR3[V555M] MSA 9 BRSK2 MSA 26 FGFR4 MSA 10 BTK MSA 27 FGFR4[N535K] MSA 10 BTK[C481S] MSA 27 FGFR4[V550E] MSA 10 BUB1/BUB3 MSA 27 FGFR4[V550L] MSA 10 CaMK1α(CAMK1) MSA 27 FGR MSA 10 CaMK1δ(CAMK1D) MSA 27 FLT1 MSA 11 CaMK2α(CAMK2A) MSA 28
    [Show full text]
  • Phosphorylation of Threonine 3 on Histone H3 by Haspin Kinase Is Required for Meiosis I in Mouse Oocytes
    ß 2014. Published by The Company of Biologists Ltd | Journal of Cell Science (2014) 127, 5066–5078 doi:10.1242/jcs.158840 RESEARCH ARTICLE Phosphorylation of threonine 3 on histone H3 by haspin kinase is required for meiosis I in mouse oocytes Alexandra L. Nguyen, Amanda S. Gentilello, Ahmed Z. Balboula*, Vibha Shrivastava, Jacob Ohring and Karen Schindler` ABSTRACT a lesser extent. However, it is not known whether haspin is required for meiosis in oocytes. To date, the only known haspin substrates Meiosis I (MI), the division that generates haploids, is prone to are threonine 3 of histone H3 (H3T3), serine 137 of macroH2A and errors that lead to aneuploidy in females. Haspin is a kinase that threonine 57 of CENP-T (Maiolica et al., 2014). Knockdown or phosphorylates histone H3 on threonine 3, thereby recruiting Aurora inhibition of haspin in mitotically dividing tissue culture cell kinase B (AURKB) and the chromosomal passenger complex lines reveal that phosphorylation of H3T3 is essential for the (CPC) to kinetochores to regulate mitosis. Haspin and AURKC, an alignment of chromosomes at the metaphase plate (Dai and AURKB homolog, are enriched in germ cells, yet their significance Higgins, 2005; Dai et al., 2005), regulation of chromosome in regulating MI is not fully understood. Using inhibitors and cohesion (Dai et al., 2009) and establishing a bipolar spindle (Dai overexpression approaches, we show a role for haspin during MI et al., 2009). In mitotic metaphase, phosphorylation of H3T3 is in mouse oocytes. Haspin-perturbed oocytes display abnormalities restricted to kinetochores, and this mark signals recruitment of the in chromosome morphology and alignment, improper kinetochore– chromosomal passenger complex (CPC) (Dai et al., 2005; Wang microtubule attachments at metaphase I and aneuploidy at et al., 2010; Yamagishi et al., 2010).
    [Show full text]
  • A New AURKC Mutation Causing Macrozoospermia
    A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis Mariem Ben Khelifa 1 2 3 , Raoudha Zouari 4 , Radu Harbuz 2 1 , Lazhar Halouani 4 , Christophe Arnoult 1 , Joël Lunardi 2 5 , Pierre F. Ray 1 2 * 1 AGIM, AGeing and IMagery, CNRS FRE3405 Université Joseph Fourier - Grenoble I , Ecole Pratique des Hautes Etudes , CNRS : UMR5525 , Faculté de médecine de Grenoble, 38700 La Tronche,FR 2 Laboratoire de biochimie et génétique moléculaire CHU Grenoble , 38043 Grenoble,FR 3 Molecular Investigation of Genetic Orphan Diseases Research Unit Institut Pasteur de Tunis , Research Unit UR04/SP03,TN 4 Clinique de la reproduction les Jasmins Clinique de la reproduction les Jasmins , 23, Av. Louis BRAILLE, 1002 Tunis,TN 5 GIN, Grenoble Institut des Neurosciences INSERM : U836 , CEA , Université Joseph Fourier - Grenoble I , CHU Grenoble , UJF - Site Santé La Tronche BP 170 38042 Grenoble Cedex 9,FR * Correspondence should be addressed to: Pierre Ray <[email protected] > Abstract The presence of close to 100% large-headed multi-tailed spermatozoa in the ejaculate has been described as a rare phenotype of male infertility with a very poor prognosis. We demonstrated previously that most cases were caused by a homozygous mutation (c.144delC) in the Aurora Kinase C gene (AURKC) leading to the absence or the production of a nonfunctional protein. AURKC deficiency in these patients blocked meiosis and resulted in the production of tetraploid spermatozoa unsuitable for fertilization. We describe here the study of two brothers presenting with large-headed spermatozoa. Molecular analysis of the AURKC gene was carried out in two brothers presenting with a typical large headed spermatozoa phenotype.
    [Show full text]
  • Maternally Recruited Aurora C Kinase Is More Stable Than Aurora B to Support Mouse Oocyte Maturation and Early Development
    Maternally recruited Aurora C kinase is more stable PNAS PLUS than Aurora B to support mouse oocyte maturation and early development Karen Schindler1,2, Olga Davydenko2, Brianna Fram, Michael A. Lampson3, and Richard M. Schultz3 Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 Edited* by John J. Eppig, The Jackson Laboratory, Bar Harbor, ME, and approved June 14, 2012 (received for review December 14, 2011) Aurora kinases are highly conserved, essential regulators of cell including abnormally condensed chromatin and abnormally division. Two Aurora kinase isoforms, A and B (AURKA and shaped acrosomes, but females were not examined (11). Muta- AURKB), are expressed ubiquitously in mammals, whereas a third tions in human AURKC cause meiotic arrest and formation of isoform, Aurora C (AURKC), is largely restricted to germ cells. tetraploid sperm (12), suggesting an essential role in cytokinesis Because AURKC is very similar to AURKB, based on sequence and in male meiosis. Experiments in mouse oocytes using a chemical functional analyses, why germ cells express AURKC is unclear. We inhibitor of AURKB (ZM447439) do not address the function of −/− report that Aurkc females are subfertile, and that AURKB func- AURKB because AURKC is also inhibited (13–17). Strategies tion declines as development progresses based on increasing se- using dominant-negative versions of AURKC are also difficult to verity of cytokinesis failure and arrested embryonic development. interpret, because the mutant may also compete with AURKB Furthermore, we find that neither Aurkb nor Aurkc is expressed (18). Overexpression studies have similar limitations because after the one-cell stage, and that AURKC is more stable during both kinases interact with inner centromere protein (INCENP) maturation than AURKB using fluorescently tagged reporter and these studies did not report expression levels of AURKB proteins.
    [Show full text]
  • Genetic Variations in AURORA Cell Cycle Kinases Are Associated With
    www.nature.com/scientificreports OPEN Genetic variations in AURORA cell cycle kinases are associated with glioblastoma multiforme Aner Mesic1, Marija Rogar2, Petra Hudler2*, Nurija Bilalovic3, Izet Eminovic1 & Radovan Komel2 Glioblastoma multiforme (GBM) is the most frequent type of primary astrocytomas. We examined the association between single nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA), Aurora kinase B (AURKB), Aurora kinase C (AURKC) and Polo-like kinase 1 (PLK1) mitotic checkpoint genes and GBM risk by qPCR genotyping. In silico analysis was performed to evaluate efects of polymorphic biological sequences on protein binding motifs. Chi-square and Fisher statistics revealed a signifcant diference in genotypes frequencies between GBM patients and controls for AURKB rs2289590 variant (p = 0.038). Association with decreased GBM risk was demonstrated for AURKB rs2289590 AC genotype (OR = 0.54; 95% CI = 0.33–0.88; p = 0.015). Furthermore, AURKC rs11084490 CG genotype was associated with lower GBM risk (OR = 0.57; 95% CI = 0.34–0.95; p = 0.031). Bioinformatic analysis of rs2289590 polymorphic region identifed additional binding site for the Yin-Yang 1 (YY1) transcription factor in the presence of C allele. Our results indicated that rs2289590 in AURKB and rs11084490 in AURKC were associated with a reduced GBM risk. The present study was performed on a less numerous but ethnically homogeneous population. Hence, future investigations in larger and multiethnic groups are needed to strengthen these results. Glioblastoma multiforme (GBM) represents the most common and lethal form of primary brain tumor with an annual incidence of 5.26 per 100,000 people 1,2 and it stands for more than 60% of all brain tumors in adults3.
    [Show full text]
  • Promising Therapy in Lung Cancer: Spotlight on Aurora Kinases
    cancers Review Promising Therapy in Lung Cancer: Spotlight on Aurora Kinases Domenico Galetta 1,* and Lourdes Cortes-Dericks 2 1 Division of Thoracic Surgery, European Institute of Oncology, IRCCS, 20141 Milan, Italy 2 Department of Biology, University of Hamburg, 20146 Hamburg, Germany; [email protected] * Correspondence: [email protected] Received: 4 September 2020; Accepted: 12 November 2020; Published: 14 November 2020 Simple Summary: Lung cancer has remained one of the major causes of death worldwide. Thus, a more effective treatment approach is essential, such as the inhibition of specific cancer-promoting molecules. Aurora kinases regulate the process of mitosis—a process of cell division that is necessary for normal cell proliferation. Dysfunction of these kinases can contribute to cancer formation. In this review, we present studies indicating the implication of Aurora kinases in tumor formation, drug resistance, and disease prognosis. The effectivity of using Aurora kinase inhibitors in the pre-clinical and clinical investigations has proven their therapeutic potential in the setting of lung cancer. This work may provide further information to broaden the development of anticancer drugs and, thus, improve the conventional lung cancer management. Abstract: Despite tremendous efforts to improve the treatment of lung cancer, prognosis still remains poor; hence, the search for efficacious therapeutic option remains a prime concern in lung cancer research. Cell cycle regulation including mitosis has emerged as an important target for cancer management. Novel pharmacological agents blocking the activities of regulatory molecules that control the functional aspects of mitosis such as Aurora kinases are now being investigated. The Aurora kinases, Aurora-A (AURKA), and Aurora B (AURKB) are overexpressed in many tumor entities such as lung cancer that correlate with poor survival, whereby their inhibition, in most cases, enhances the efficacy of chemo-and radiotherapies, indicating their implication in cancer therapy.
    [Show full text]
  • Kinome Expression Profiling to Target New Therapeutic Avenues in Multiple Myeloma
    Plasma Cell DIsorders SUPPLEMENTARY APPENDIX Kinome expression profiling to target new therapeutic avenues in multiple myeloma Hugues de Boussac, 1 Angélique Bruyer, 1 Michel Jourdan, 1 Anke Maes, 2 Nicolas Robert, 3 Claire Gourzones, 1 Laure Vincent, 4 Anja Seckinger, 5,6 Guillaume Cartron, 4,7,8 Dirk Hose, 5,6 Elke De Bruyne, 2 Alboukadel Kassambara, 1 Philippe Pasero 1 and Jérôme Moreaux 1,3,8 1IGH, CNRS, Université de Montpellier, Montpellier, France; 2Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium; 3CHU Montpellier, Laboratory for Monitoring Innovative Therapies, Department of Biologi - cal Hematology, Montpellier, France; 4CHU Montpellier, Department of Clinical Hematology, Montpellier, France; 5Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany; 6Nationales Centrum für Tumorerkrankungen, Heidelberg , Ger - many; 7Université de Montpellier, UMR CNRS 5235, Montpellier, France and 8 Université de Montpellier, UFR de Médecine, Montpel - lier, France ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2018.208306 Received: October 5, 2018. Accepted: July 5, 2019. Pre-published: July 9, 2019. Correspondence: JEROME MOREAUX - [email protected] Supplementary experiment procedures Kinome Index A list of 661 genes of kinases or kinases related have been extracted from literature9, and challenged in the HM cohort for OS prognostic values The prognostic value of each of the genes was computed using maximally selected rank test from R package MaxStat. After Benjamini Hochberg multiple testing correction a list of 104 significant prognostic genes has been extracted. This second list has then been challenged for similar prognosis value in the UAMS-TT2 validation cohort.
    [Show full text]
  • Identification of Aurora Kinase B and Wee1-Like Protein Kinase As
    The American Journal of Pathology, Vol. 182, No. 4, April 2013 ajp.amjpathol.org BIOMARKERS, GENOMICS, PROTEOMICS, AND GENE REGULATION Identification of Aurora Kinase B and Wee1-Like Protein Kinase as Downstream Targets of V600EB-RAF in Melanoma Arati Sharma,*yz SubbaRao V. Madhunapantula,*yz Raghavendra Gowda,*yz Arthur Berg,x Rogerio I. Neves,*yz{k and Gavin P. Robertson*yz{k** From the Departments of Pharmacology,* Public Health Sciences,x Surgery,{ Dermatologyk and Pathology,** the Melanoma Center,y and the Melanoma Therapeutics Program,z Pennsylvania State University College of Medicine, Hershey, Pennsylvania Accepted for publication December 21, 2012. BRAF is the most mutated gene in melanoma, with approximately 50% of patients containing V600E mutant protein. V600EB-RAF can be targeted using pharmacological agents, but resistance develops in Address correspondence to Gavin P. Robertson, Ph.D., patients by activating other proteins in the signaling pathway. Identifying downstream members in this Department of Pharmacology, signaling cascade is important to design strategies to avoid the development of resistance. Unfortu- Pennsylvania State University nately, downstream proteins remain to be identified and therapeutic potential requires validation. A V600E College of Medicine, 500 kinase screen was undertaken to identify downstream targets in the B-RAF signaling cascade. University Dr., Hershey, Involvement of aurora kinase B (AURKB) and Wee1-like protein kinase (WEE1) as downstream proteins in PA 17033. E-mail: the V600EB-RAF pathway was validated in xenografted tumors, and mechanisms of action were charac- [email protected]. terized in size- and time-matched tumors. Levels of only AURKB and WEE1 decreased in melanoma cells, when V600EB-RAF, mitogen-activated protein kinase 1/2, or extracellular signaleregulated kinase 1/2 protein levels were reduced using siRNA compared with other identified kinases.
    [Show full text]
  • Aurora Kinase B Inhibition: a Potential Therapeutic Strategy for Cancer
    molecules Review Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for Cancer Naheed Arfin Borah 1,2 and Mamatha M. Reddy 1,2,* 1 The Operation Eyesight Universal Institute for Eye Cancer, L.V. Prasad Eye Institute, Bhubaneswar 751024, India; [email protected] 2 School of Biotechnology, KIIT University, Bhubaneswar 751024, India * Correspondence: [email protected] or [email protected]; Tel.: +91-6743987175 Abstract: Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression. Deregulation of AURKB is observed in several tumors and its overexpression is frequently linked to tumor cell invasion, metastasis and drug resistance. AURKB has emerged as an attractive drug target leading to the development of small molecule inhibitors. This review summarizes recent findings pertaining to the role of AURKB in tumor development, therapy related drug resistance, and its inhibition as a potential therapeutic strategy for cancer. We discuss AURKB inhibitors that are in preclinical and clinical development and combination studies of AURKB inhibition with other therapeutic strategies. Keywords: aurora kinase B (AURKB); cancer; AURKB regulation; AURKB inhibitors; therapy related drug resistance; combination therapy Citation: Borah, N.A.; Reddy, M.M. Aurora Kinase B Inhibition: A Potential Therapeutic Strategy for 1. Introduction Cancer. Molecules 2021, 26, 1981. Aurora kinases (AURKs) are protein serine/threonine kinases consisting of three https://doi.org/10.3390/ members in the gene family—aurora kinase A (AURKA), aurora kinase B (AURKB) and molecules26071981 aurora kinase C (AURKC) [1].
    [Show full text]
  • Haspin Inhibition Reveals Functional Differences of Interchromatid Axis–Localized AURKB and AURKC
    M BoC | BRIEF REPORT Haspin inhibition reveals functional differences of interchromatid axis–localized AURKB and AURKC Suzanne M. Quartuccio, Shweta S. Dipali, and Karen Schindler* Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 ABSTRACT Aneuploidy is the leading genetic abnormality contributing to infertility, and Monitoring Editor chromosome segregation errors are common during female mammalian meiosis I (MI). Previ- Kerry S. Bloom ous results indicate that haspin kinase regulates resumption of meiosis from prophase arrest, University of North Carolina chromosome condensation, and kinetochore–microtubule attachments during early prometa- Received: Dec 13, 2016 phase of MI. Here we report that haspin inhibition in late prometaphase I causes acceleration Revised: Jun 16, 2017 of MI, bypass of the spindle assembly checkpoint (SAC), and loss of interchromatid axis– Accepted: Jun 20, 2017 localized Aurora kinase C. Meiotic cells contain a second chromosomal passenger complex (CPC) population, with Aurora kinase B (AURKB) bound to INCENP. Haspin inhibition in oo- cytes from Aurkc−/− mice, where AURKB is the sole CPC kinase, does not alter MI completion timing, and no change in localization of the SAC protein, MAD2, is observed. These data suggest that AURKB on the interchromatid axis is not needed for SAC activation and illus- trate a key difference between the functional capacities of the two AURK homologues. INTRODUCTION Infertility is a common health problem affecting 6.7 million women (Higgins, 2003), first identified in mouse spermatocytes (Tanaka in the United States and 80 million people worldwide (World Health et al., 1999), that phosphorylates histone H3 at threonine 3 (H3T3; Organization, 1991).
    [Show full text]