STUB1 Rabbit Pab

Total Page：16

File Type：pdf, Size：1020Kb

Leader in Biomolecular Solutions for Life Science STUB1 Rabbit pAb Catalog No.: A11751 1 Publications Basic Information Background Catalog No. This gene encodes a protein containing tetratricopeptide repeat and a U-box that A11751 functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), Observed MW among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal 36kDa recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. Calculated MW 27kDa/34kDa Category Primary antibody Applications WB, IF, IP Cross-Reactivity Human, Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 10273 Q9UNE7 IF 1:50 - 1:200 Immunogen 1:50 - 1:200 IP Recombinant fusion protein containing a sequence corresponding to amino acids 1-303 of human STUB1 (NP_005852.2). Synonyms STUB1;CHIP;HSPABP2;NY-CO-7;SCAR16;SDCCAG7;UBOX1 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using STUB1 Antibody (A11751) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. Detection: ECL Basic Kit (RM00020). Exposure time: 30s. Immunoprecipitation analysis of 300ug extracts of HeLa cells using 3ug STUB1 antibody (A11751). Western blot was performed from the immunoprecipitate using STUB1 antibody (A11751) at a dilition of 1:1000. Immunofluorescence analysis of C6 cells Immunofluorescence analysis of L929 cells Immunofluorescence analysis of U-2 OS using STUB1 Polyclonal Antibody (A11751) using STUB1 Polyclonal Antibody (A11751) cells using STUB1 Polyclonal Antibody at dilution of 1:100 (40x lens). Blue: DAPI at dilution of 1:100 (40x lens). Blue: DAPI (A11751) at dilution of 1:100 (40x lens). for nuclear staining. for nuclear staining. Blue: DAPI for nuclear staining. Antibody | Protein | ELISA Kits | Enzyme | NGS | Service For research use only. Not for therapeutic or diagnostic purposes. Please visit http://abclonal.com for a complete listing of recommended products..

Copy Link

Recommended publications

STUB1 / CHIP Antibody Rabbit Polyclonal Antibody Catalog # ALS16226
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 STUB1 / CHIP Antibody Rabbit Polyclonal Antibody Catalog # ALS16226 Specification STUB1 / CHIP Antibody - Product Information Application WB Primary Accession Q9UNE7 Reactivity Human Host Rabbit Clonality Polyclonal Calculated MW 35kDa KDa STUB1 / CHIP Antibody - Additional Information Sample (30 ug of whole cell lysate) A: 293T Gene ID 10273 10% SDS PAGE STUB1 antibody diluted at 1:10000 Other Names E3 ubiquitin-protein ligase CHIP, 6.3.2.-, Antigen NY-CO-7, CLL-associated antigen STUB1 / CHIP Antibody - Background KW-8, Carboxy terminus of Hsp70-interacting protein, STIP1 homology and U box-containing protein 1 E3 ubiquitin-protein ligase which targets {ECO:0000312|HGNC:HGNC:11427}, STUB1 misfolded chaperone substrates towards (<a href="http://www.genenames.org/cgi-bi proteasomal degradation. Collaborates with n/gene_symbol_report?hgnc_id=11427" ATXN3 in the degradation of misfolded target="_blank">HGNC:11427</a>) chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to Target/Specificity STUB1/CHIP substrates and preventing further Human STUB1 chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity Reconstitution & Storage of several chaperone complexes, including Keep as concentrated solution. Aliquot and Hsp70, Hsc70 and Hsp90. Mediates transfer of store at -20°C or below. Avoid multiple non-canonical short ubiquitin chains to HSPA8 freeze-thaw cycles. that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase Precautions beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', STUB1 / CHIP Antibody is for research use thereby playing a role in base-excision repair: only and not for use in diagnostic or catalyzes polyubiquitination by amplifying the therapeutic procedures.
[Show full text]
The Functions of CHIP in Age Related Disease
Central JSM Enzymology and Protein Science Bringing Excellence in Open Access Review Article *Corresponding author Kathryn L Ball, The Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research Centre, The Functions of CHIP in Age University of Edinburgh, Western General Hospital, Crewe Road South, EH4 2XR, UK, Tel: +44 0-131-651-8500; E-mail: Related Disease Submitted: 03 August 2016 Ball KL*, Ning J, Nita E, and Dias C Accepted: 29 September 2016 Institute of Genetics and Molecular Medicine, University of Edinburgh, UK Published: 01 October 2016 Copyright Abstract © 2016 Ball et al. CHIP is a key component of the protein homeostasis or ‘Proteostasis’ network OPEN ACCESS that maintains protein structure and function as a way to ensure the integrity of the proteome in individual cells and the health of the whole organism. Proteostasis Keywords influences the biogenesis, folding, trafficking and degradation of proteins. Originally • CHIP identified as a Hsc70 associated protein and a co-chaperone CHIP has E3-ubiquitin • E3-ligase ligase activity and also displays an intrinsic chaperoning ability. It has become clear • Chaperone that CHIP is a multi-functional protein with roles in cellular processes that go beyond • Structure function its co-chaperone activity. Not surprisingly, by unravelling the functions of CHIP, we are • Neurodegeneration beginning to appreciate that loss of CHIP’s integrity can lead to the development of • Cancer several serious pathological conditions. Here we will describe the key features of CHIPs structure and functions with an emphasis on the non-canonical activities of CHIP before concentrating on the role it plays in protecting against the age associated pathologies of neurodegeneration and cancer.
[Show full text]
Kinase SH3 NH2 Cdc42
A Dissertation The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed Lineage Kinase 3 and Mixed Lineage Kinase 4 Beta by Natalya A. Blessing Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology _________________________________________ Dr. Deborah Chadee, Committee Chair _________________________________________ Dr. Richard Komuniecki, Committee Member _________________________________________ Dr. Malathi Krishnamurthy, Committee Member _________________________________________ Dr. Frank Pizza, Committee Member _________________________________________ Dr. Don Ronning, Committee Member _________________________________________ Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo May 2015 Copyright 2015, Natalya A. Blessing This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The E3 Ligase CHIP Mediates Ubiquitination and Degradation of Mixed Lineage Kinase 3 and Mixed Lineage Kinase 4 Beta by Natalya Blessing Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Biology The University of Toledo May 2015 The mixed lineage kinases (MLKs) are serine/threonine mitogen-activated protein kinase kinase kinases (MAP3Ks) that modulate the activities of extracellular signal- regulated kinase, c-Jun N-terminal kinase, and p38 signaling pathways. MLK3 plays a pivotal role in cell invasion, tumorigenesis and metastasis. Wild type MLK4 negatively regulates MAPK signaling by possibly inhibiting MLK3 activation, while mutant MLK4 plays in important role in driving colorectal cancer and glioblastomal tumorigenesis (Martini et al., 2013). The mechanisms by which MLK3 and MLK4 protein levels are regulated in cells are unknown. The carboxyl terminus of HSC-70 interacting protein (CHIP) is a U-box E3 ubiquitin ligase that regulates cytosolic protein degradation in response to stress.
[Show full text]
STUB1 Mutations in Autosomal Recessive Ataxias
Heimdal et al. Orphanet Journal of Rare Diseases 2014, 9:146 http://www.ojrd.com/content/9/1/146 RESEARCH Open Access STUB1 mutations in autosomal recessive ataxias – evidence for mutation-specific clinical heterogeneity Ketil Heimdal1*, Monica Sanchez-Guixé2,3, Ingvild Aukrust2, Jens Bollerslev4,5, Ove Bruland2, Greg Eigner Jablonski6, Anne Kjersti Erichsen7, Einar Gude8, Jeanette A Koht9, Sigrid Erdal2, Torunn Fiskerstrand2,3, Bjørn Ivar Haukanes2, Helge Boman2, Lise Bjørkhaug10, Chantal ME Tallaksen11,12, Per M Knappskog2,13† and Stefan Johansson2,13† Abstract Background: A subset of hereditary cerebellar ataxias is inherited as autosomal recessive traits (ARCAs). Classification of recessive ataxias due to phenotypic differences in the cerebellum and cerebellar structures is constantly evolving due to new identified disease genes. Recently, reports have linked mutations in genes involved in ubiquitination (RNF216, OTUD4, STUB1) to ARCA with hypogonadism. Methods and results: With a combination of homozygozity mapping and exome sequencing, we identified three mutations in STUB1 in two families with ARCA and cognitive impairment; a homozygous missense variant (c.194A > G, p.Asn65Ser) that segregated in three affected siblings, and a missense change (c.82G > A, p.Glu28Lys) which was inherited in trans with a nonsense mutation (c.430A > T, p.Lys144Ter) in another patient. STUB1 encodes CHIP (C-terminus of Heat shock protein 70 – Interacting Protein), a dual function protein with a role in ubiquitination as a co-chaperone with heat shock proteins, and as an E3 ligase. We show that the p.Asn65Ser substitution impairs CHIP’s ability to ubiquitinate HSC70 in vitro, despite being able to self-ubiquitinate.
[Show full text]
Aggresomal Sequestration and STUB1-Mediated Ubiquitylation During Mammalian Proteaphagy of Inhibited Proteasomes
Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes Won Hoon Choia,b, Yejin Yuna,b, Seoyoung Parka,c, Jun Hyoung Jeona,b, Jeeyoung Leea,b, Jung Hoon Leea,c, Su-A Yangd, Nak-Kyoon Kime, Chan Hoon Jungb, Yong Tae Kwonb, Dohyun Hanf, Sang Min Lime, and Min Jae Leea,b,c,1 aDepartment of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 03080 Seoul, Korea; bDepartment of Biomedical Sciences, Seoul National University Graduate School, 03080 Seoul, Korea; cNeuroscience Research Institute, Seoul National University College of Medicine, 03080 Seoul, Korea; dScience Division, Tomocube, 34109 Daejeon, Korea; eConvergence Research Center for Diagnosis, Korea Institute of Science and Technology, 02792 Seoul, Korea; and fProteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, 03080 Seoul, Korea Edited by Richard D. Vierstra, Washington University in St. Louis, St. Louis, MO, and approved July 1, 2020 (received for review November 18, 2019) The 26S proteasome, a self-compartmentalized protease complex, additional LC3-interacting region; the target cargoes can be plays a crucial role in protein quality control. Multiple levels of docked onto phosphatidylethanolamine-modified LC3 (LC3-II) regulatory systems modulate proteasomal activity for substrate on the expanding phagophore membrane, enveloped by an hydrolysis. However, the destruction mechanism of mammalian autophagosome, and eventually degraded in the autolysosomes. proteasomes is poorly understood. We found that inhibited pro- Notably, the enzymatic cascade attaching the lipid moiety at the teasomes are sequestered into the insoluble aggresome via C-terminal glycine of the cleaved LC3 protein in autophagy re- HDAC6- and dynein-mediated transport.
[Show full text]
STUB1 Suppresseses Tumorigenesis and Chemoresistance Through Antagonizing YAP1 Signaling
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Digital Commons@Becker Washington University School of Medicine Digital Commons@Becker Open Access Publications 10-1-2019 STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling Dong-E Tang Yong Dai Lie-Wen Lin Yong Xu Dong-Zhou Liu See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Authors Dong-E Tang, Yong Dai, Lie-Wen Lin, Yong Xu, Dong-Zhou Liu, Xiao-Ping Hong, Hao-Wu Jiang, and Song- Hui Xu Received: 5 June 2019 | Revised: 29 July 2019 | Accepted: 5 August 2019 DOI: 10.1111/cas.14166 ORIGINAL ARTICLE STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling Dong‐E Tang1 | Yong Dai1 | Lie‐Wen Lin1 | Yong Xu1 | Dong‐Zhou Liu1 | Xiao‐Ping Hong1 | Hao‐Wu Jiang2 | Song‐Hui Xu1,3 1Department of Clinical Medical Research Center, The Second Clinical Medical College Abstract of Jinan University, The First Affiliated Yes‐associated protein (YAP) is a component of the canonical Hippo signaling path‐ Hospital Southern, University of Science and Technology, Shenzhen People's Hospital, way that is known to play essential roles in modulating organ size, development, and Shenzhen, China tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell 2 Department of Anesthesiology and Center survival and chemoresistance, has been verified in different types of human cancers. for the Study of Itch, Washington University School of Medicine, St. Louis, MO, USA However, the molecular mechanism of YAP1 upregulation in cancer is still unclear.
[Show full text]
The Importance of Regulatory Ubiquitination in Cancer and Metastasis
CELL CYCLE 2017, VOL. 16, NO. 7, 634–648 http://dx.doi.org/10.1080/15384101.2017.1288326 REVIEW The importance of regulatory ubiquitination in cancer and metastasis L. H. Galloa,J.Koa, and D. J. Donoghuea,b aDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA; bMoores UCSD Cancer Center, University of California San Diego, La Jolla, CA, USA ABSTRACT ARTICLE HISTORY Ubiquitination serves as a degradation mechanism of proteins, but is involved in additional cellular Received 9 December 2016 processes such as activation of NFkBinﬂammatory response and DNA damage repair. We highlight the E2 Revised 20 January 2017 ubiquitin conjugating enzymes, E3 ubiquitin ligases and Deubiquitinases that support the metastasis of a Accepted 24 January 2017 plethora of cancers. E3 ubiquitin ligases also modulate pluripotent cancer stem cells attributed to KEYWORDS chemotherapy resistance. We further describe mutations in E3 ubiquitin ligases that support tumor deubiquitinase; ligase; proliferation and adaptation to hypoxia. Thus, this review describes how tumors exploit members of the metastasis; ubiquitination vast ubiquitin signaling pathways to support aberrant oncogenic signaling for survival and metastasis. Ubiquitination signaling overview The challenging route to metastasis Ubiquitin (Ub), a highly conserved 76-amino acid protein Cancer progression eventually may lead to metastasis, which is expressed in all cell types, has 7 lysine residues (K6, K11, the ﬁnal stage responsible for more than 90% of all terminal K27, K29, K33, K48, K63) that can be polymerized into var- cancer deaths. Various genomic abnormalities must be present ious linkages. The resulting linkage of Ub chains creates a to allow cells of a primary tumor to ignore apoptotic signals, certain topology that can be sampled by interacting proteins proliferate and survive.
[Show full text]
Stabilization of Notch1 by the Hsp90 Chaperone Is Crucial for T-Cell
Published OnlineFirst January 31, 2017; DOI: 10.1158/1078-0432.CCR-16-2880 Biology of Human Tumors Clinical Cancer Research Stabilization of Notch1 by the Hsp90 Chaperone is Crucial for T-Cell Leukemogenesis Zhaojing Wang1,2,3, Yufeng Hu3, Daibiao Xiao2, Jingchao Wang2, Chuntao Liu3, Yisheng Xu4, Xiaomeng Shi4, Peng Jiang5, Liang Huang6, Peng Li7, Hudan Liu1,2, and Guoliang Qing1,2 Abstract Purpose: Notch1 deregulation is assuming a focal role in T-cell Results: We identify the Hsp90 chaperone as a direct ICN1- acute lymphoblastic leukemia (T-ALL). Despite tremendous binding partner essential for its stabilization and transcrip- advances in our understanding of Notch1 transcriptional pro- tional activity. T-ALL cells exhibit constitutive endogenous grams, the mechanisms by which Notch1 stability and turnover ICN1–Hsp90 interaction and Hsp90 depletion markedly are regulated remain obscure. The goal of the current study is to decreases ICN1 levels. The Hsp90-associated E3 ubiquitin identify intracellular Notch1 (ICN1, the activated form of ligase Stub1 mediates the ensuring proteasome-dependent Notch1) binding partner(s) regulating its stability and activity. ICN1 degradation. Administration of 17-AAG or PU-H71, two Experimental Design: We employed immunoafﬁnity puriﬁ- distinct Hsp90 inhibitors, depletes ICN1, inhibits T-ALL cell cation to identify ICN1-associating partner(s) and used coim- proliferation, and triggers dramatic apoptotic cell death. Sys- munoprecipitation to verify the endogenous protein interac- temic treatment with PU-H71 reduces ICN1 expression and tion. Pharmacologic or short hairpin RNA–mediated inhibition profoundly inhibits murine T-ALL allografts as well as human was applied in loss-of-function assays to assess the role of T-ALL xenografts.
[Show full text]
STUB1/CHIP Antibody Order 021-34695924 [email protected] Support 400-6123-828 50Ul [email protected] 100 Ul √ √ Web
TA6514 STUB1/CHIP Antibody Order 021-34695924 [email protected] Support 400-6123-828 50ul [email protected] 100 uL √ √ Web www.ab-mart.com.cn Description: E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1- dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation. Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B- dependent manner. Likely mediates polyubiquitination and downregulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation. May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation.
[Show full text]
The Ubiquitin Ligase Stub1 Negatively Modulates Regulatory T Cell Suppressive Activity by Promoting Degradation of the Transcription Factor Foxp3
Immunity Article The Ubiquitin Ligase Stub1 Negatively Modulates Regulatory T Cell Suppressive Activity by Promoting Degradation of the Transcription Factor Foxp3 Zuojia Chen,1,12 Joseph Barbi,2,12 Shurui Bu,2,3,12 Huang-Yu Yang,2,4 Zhiyuan Li,1 Yayi Gao,1 Dilini Jinasena,2 Juan Fu,2 Fang Lin,1 Chen Chen,1 Jing Zhang,1 Ning Yu,8 Xiangpei Li,8 Zhao Shan,1 Jia Nie,1 Zhimei Gao,1 Hong Tian,11 Yangyang Li,1 Zhengju Yao,1 Ying Zheng,2 Benjamin V. Park,2 Ziyi Pan,2 Jing Zhang,2 Eric Dang,2 Zhiguang Li,2 Honglin Wang,9 Weibo Luo,10 Liwu Li,11 Gregg L. Semenza,10 Song-Guo Zheng,5 Karin Loser,6 Andy Tsun,1 Mark I. Greene,7 Drew M. Pardoll,2 Fan Pan,2,* and Bin Li1,* 1Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China 2Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA 3Department of Gastroenterology, Afﬁliated Jinshan Hospital, Fudan University, Shanghai 201508, China 4Department of Nephrology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 333, Taiwan 5Division of Rheumatology, Department of Medicine, Penn State University College of Medicine, Hershey, PA 17033, USA 6Department of Dermatology, University of Mu¨ nster, D-48149 Mu¨ nster, Germany 7Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadephia,
[Show full text]
Dynamic Chromatin Associated Ubiquitination with Cell Cycle
Dynamic chromatin associated ubiquitination with cell cycle progression in human cancer cells DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Mansi Shyam Arora Graduate Program in Molecular, Cellular and Developmental Biology The Ohio State University 2014 Dissertation Committee: Dr. Jeffrey Parvin, Advisor Dr. Anita Hopper Dr. Mark Parthun Dr. Robin Wharton Copyright by Mansi Shyam Arora 2014 Abstract In this dissertation work, we have analyzed the pattern of ubiquitin conjugates on human chromatin and its changes with the progression of cell cycle. Our work shows that during interphase, ubiquitination marks the transcribed regions of the genome. This ubiquitination correlates with the ubiquitination of H2B, is dependent on active transcription and is removed during mitosis. We had anticipated that all the ubiquitin associated with the transcribed regions would be removed from chromatin during mitosis, but contrary to our expectation, we found that at the promoters of active genes chromatin ubiquitination levels actually increase thus implying this modification as a possible mitotic bookmark. In the second half of this project, we set out to identify the substrate modified by this post translational modification at these promoters and the enzymes involved in its deposition and removal before and after mitosis respectively. Our results show the surprising involvement of the SAGA associated deubiquitinase USP22 and the polycomb complex proteins BMI1 and RING1A in the regulation of this bookmark during mitosis. The polycomb complex proteins are thought to primarily regulate gene expression by transcriptional repression. Although some previous studies have implied the involvement ii of the polycomb proteins in the regulation of active genes, their association with the transcriptional regulation of active genes during the mitosis to G1 transition has not been described before this work.
[Show full text]
High HSPA8 Expression Predicts Adverse Outcomes of Acute Myeloid Leukemia Jun Li1 and Zheng Ge1,2*
Li and Ge BMC Cancer (2021) 21:475 https://doi.org/10.1186/s12885-021-08193-w RESEARCH Open Access High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia Jun Li1 and Zheng Ge1,2* Abstract Background: Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods: In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN- AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results: HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA).
[Show full text]