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This is a free sample of content from Protein Homeostasis, Second Edition. Click here for more information on how to buy the book. Index A overview of diseases, 13, 41–43 Abf2, 160 polyphosphate AD. See Alzheimer’s disease amyloidogenic protein interactions, 393–395 AFG3L2, 162 cytotoxicity amelioration, 396–397 Africa swine fever virus (ASFV), 468 prospects for study, 52, 55 Aging protein homeostasis context, 48–49 heat shock factors, 431 structure–activity relationship, 14–15 proteostasis network regulation, 450–452 therapeutic intervention, 50–52 Ago2, 335, 467 toxicity, 47–48 Aha1, 333, 335, 338–339, 504 Amyotrophic lateral sclerosis (ALS), 214, 262, 264, AIRAP, 267 290–291, 293, 404, 409, 524, 532 AIRAPL, 267–268 ApoB, 135 AKT, 274, 467 ASFV. See Africa swine fever virus ALK, 503 ATAD1, 104 ALMC2, 487 ATF4, 79, 88, 182, 186, 189, 445–446 ALP. See Autophagy lysosome pathway ATF5, 182, 186, 189 a-Synuclein, 375, 522 ATF6, 60, 62–64, 79, 445–446, 481–482, 484–489 ALS. See Amyotrophic lateral sclerosis ATFS-1, 99, 180–181, 185, 188–189, 445–446 Alzheimer’s disease (AD), 186, 519 Atg7, 293 autophagy lysosomal pathway, 290–291 Atg32, 167 chaperone studies, 213–214, 216–217, 222 ATM, 313 Hsp90 studies, 337 ATR, 313 polyphosphate studies, 392, 394–395, 399 Atropine, 501 AMPK, 444 ATXN2, 524 Amyloid Autophagy lysosome pathway (ALP) chaperone modulation chaperone-mediated autophagy, 288–289 aggregation prevention, 217–222 history of study, 285 degradation of amyloid-forming proteins, 225–227 macroautophagy, 287–288 disaggregation of amyloids, 223–225 microautophagy, 288 fibril spreading, 227–229 neurodegenerative disease, 290–294 neutralization/detoxification of aggregates, proteostasis network, 289 222–223 therapeutic targeting, 294–295 overview, 216 prospects for study, 229 quality control, 216–217 B characteristics, 42–44 BAG1, 225–226 formation kinetics and mechanisms, 44–47 BAG2, 200 functional amyloids Bag2, 462 bacteria, 22–23 Bag3, 463 biofilms, 23–24 BAG4, 223 classification, 15–22 Bag6, 103 curli, 23–27 BAP, 466 disease amyloid comparison, 32–34 BCR-ABL, 498, 501 HET-s, 22, 30–32 b-Solenoid, 30 peptide hormones b-TRCP, 269 aggregation in Golgi, 27–28 BiP, 63–64, 68–70, 79, 81–83, 99, 115, 118, 128–130, membrane formation, 28–29 132–133, 217, 221, 462, 466, 485 release, 29–30 BIRC5, 467 storage in Golgi, 28–29 BIX, 485 neurodegenerative diseases, 214–216 Blm10, 272 545 © 2019 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Protein Homeostasis, Second Edition. Click here for more information on how to buy the book. Index BMRF1, 463 CsgD, 24 BRICHOS domain proteins, 222 CsgE, 24 Brown adipose tissue, 444 CsgF, 24 CsgG, 24, 27 CST, 312 C Cue5, 271 CaMKII, 276 Curli, 23–27 CamSol Cushing’s disease, 339 aggregation-promoting hotspot identification, 6–7 Cyclin B, 274 biophysical prediction of protein solubility, 3–6 Cyp40, 332, 338 design of protein mutants with enhanced solubility, 7 Cytomegalovirus (CMV), 135, 463, 465 protein variant library screening, 6 proteome-wide predictions of solubility, 9–11 solubility profile D intrinsic, 4 DAF-16, 445, 449–450 structurally corrected profile, 4–6 DARS2, 160 solubility score, 6 Ddi1, 262 stability versus solubility trade-offs, 7–9 DDI2, 270 CAP80, 468 Ddx4, 408 Carboxypeptidase Y (CPY), 101, 107 Dengue virus, 462, 465–466, 470 CASA. See Chaperone-assisted selective autophagy DFCP1, 288 Casein kinase, 179 Diabetes, amyloid, 522, 536 CBEP, 22 DIABLO, 168 CCHFV. See Crimean-Congo hemorrhagic fever virus Djp1, 106 CCT, 315, 445, 465–466 DnaJ, 86, 306–307, 462 Cdc37, 331–332, 334–336, 339, 464, 467 DNAJA1, 224 Cdc48, 134, 267 DNAJA2, 224 Cdk4, 332 DNAJB1, 223–224 Ceapins, 488 DNAJB6, 221, 463 CFTR, 135, 140–141, 338 DNAJB8, 221 Chaperone-assisted selective autophagy (CASA), 201, 227 DNAJB11, 462 Chaperone-mediated autophagy (CMA), 201, 288–289 DNAJC5, 227 Chikungunya virus, 470 DNAJC6, 228 CHIP, 441, 464, 505 DNAJC13, 229 CHMP2B, 294 DNAJC14, 466 CHOP, 88–90, 182, 189 DNAJC19, 165 Cis1, 105 DnaK, 306–307, 422 CL1, 105 Doa10, 101 CLEAR, 287 DP1, 330 CLEC-41, 449 DP2, 330 ClpA, 373 DRP1, 163–164 ClpB, 373–374, 376–382, 384 DsbC, 123 ClpC, 373 DsbD, 123 ClpP, 160, 163, 373 Dsk2, 104, 262, 266–267 ClpX, 373 CLPXP, 160, 162 CMA. See Chaperone-mediated autophagy E CMV. See Cytomegalovirus EBV. See Epstein–Barr virus CNPY3, 323 Ecm29, 275 Cns1, 332 EDEM, 118–119, 130–131 COX, 162 EGFR, 504 Cpr6, 333 eIF2, 88–90, 183 Cpr7, 332 EnaC, 141 CPY. See Carboxypeptidase Y Endoplasmic reticulum (ER). See also Unfolded protein Crimean-Congo hemorrhagic fever virus (CCHFV), 467 response Crystallins. See HSPB4; HSPB5 protein folding, 59–60 CsgA, 24–26, 33, 393 redox regulation CsgB, 24–25, 33 calcium homeostasis, 120–122 CsgC, 24 Erdj5 quality control, 118–120 546 © 2019 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Protein Homeostasis, Second Edition. Click here for more information on how to buy the book. Index oxidative folding, 115–118 H prospects for study, 122–123 HAC1, 62, 77, 79 redox environment, 113–114 HBV. See Hepatitis B virus Endoplasmic reticulum–associated degradation (ERAD) Hch1, 333 diseases, 135–140 HCV. See Hepatitis C virus overview, 60, 69, 484 HD. See Huntington’s disease prospects for study, 140–141 HDAC3, 315 protein abundance regulation, 134–135 HDAC6, 223 quality control, 118–120, 131–134 HDAC7, 442 substrate recognition, 135 HDAC9, 442 Epstein–Barr virus (EBV), 463, 467, 470 Hdj1, 86, 442 ER. See Endoplasmic reticulum Heat shock factors (HSFs). See also specific factors ERAD. See Endoplasmic reticulum–associated functions degradation development, 428–430 ERAL1, 160 metabolism, 430 Erdj4, 86 interplay between factors, 427–428 Erdj5, 114, 118–121, 130 overview, 422 ERK, 468, 504, 507 pathology ERK1, 443 cancer, 430–431 ERK2, 287 degeneration and aging, 431 Ero1, 115–117 posttranslational modifications, 425 promoter architecture, 427 prospects for study, 431–432 F structure, 422–425 FapA, 27 Hepatitis B virus (HBV), 464–467, 470 FapB, 27 Hepatitis C virus (HCV), 462–463, 465, 469–470 FapC, 23, 25–27, 33 HER2, 503 FapE, 27 HERP, 133 FapF, 27 Herpes simplex virus (HSV), 463, 470 FASD. See Fetal alcohol spectrum disorder HET-s, 22, 30–34 FBXW7, 269, 426, 443 HIV. See Human immunodeficiency virus Fetal alcohol spectrum disorder (FASD), 429 HMG-CoA reductase, 134 FGF21, 183, 185 hnRNPA1, 375 FICD, 82–83 hnRNPA2, 375 FK506. See Tacrolimus HOP, 503, 505 FKBP8, 464 Hop, 330, 333, 338 FKBP12, 290, 526 HPIV. See Human parainfluenza virus FKBP51, 332, 338–339 HPV. See Human papillomavirus FKBP52, 332, 338–339 HRD1, 268 FLP-2, 183 Hrd1, 133 FOXA, 445, 449 Hrd3, 133 FOXO, 445, 449 HRI, 182 FUNDC1, 168 Hsc82, 322 FUS, 375, 406, 409–410, 412, 450, 532 HSF1 aging studies, 431 cancer studies, 511 G developmental control and tissue-specific responses, GADD34, 88 428–430, 444–445 GCN2, 186 heat shock response, stress resilience, and proteostasis, GDF15, 184 441–444 Get3, 97 Hsp70 interactions, 308 Glutathione, 114–115, 117, 121 Hsp90 regulation, 329, 503 Glutathione peroxidase, 115 interaction with other heat shock factors, 427–428 GroEL, 308, 313–315, 468 metabolism function, 430 GroES, 314, 468 organismal level cell stress responses, 445–446 Grp94, 130, 322–323, 326, 330, 496 posttranslational regulation, 425–426 Grp170, 462 promoter, 427 GrpE, 307 structure, 422 GSK3b, 443 virus replication cycle, 461 547 © 2019 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Protein Homeostasis, Second Edition. Click here for more information on how to buy the book. Index HSF2, 422, 425–431 Hsp104, disaggregation mechanism plasticity, 383–384 HSF3, 422 Hsp105 HSF4, 422, 425, 427, 429–430 overview, 106, 200, 374–376, 462 HSF5, 422 substrate engagement and release, 380–383 HSFs. See Heat shock factors substrate translocation, 376–380 HSFs. See Heat shock factors Hsp110, 135, 200, 217, 226, 224–225, 374 HSFX, 422 HSPA5. See BiP HSFY, 422 HSPA8, 223–228 Hsj2, 463 HSPB1, 222, 354, 356, 358–364, 467–468 HSP8A, 288 HSPB2, 356–357, 360 Hsp10, 178 HSPB3, 356–357, 360 Hsp26, 414 HSPB4, 353–354, 356, 360–362, 364 Hsp33, 414 HSPB5, 222 Hsp40, 128–129, 133, 199, 240, 249 HSPB5, 353–354, 356, 358–363 Hsp42, 414 HSPB6, 354, 357–358 Hsp47, 69 HSPB7, 360 Hsp60, 178, 199, 313–315 HSPB8, 354, 360 Hsp70. See also specific family members HSV. See Herpes simplex virus amyloid detoxification, 223, 225–226 HTLV. See Human T-lymphotropic virus endoplasmic reticulum–associated degradation, HtpG, 326 128–129 HtrA1, 375 overview, 199–200, 216–217, 306–309 Hul5, 274–275 ribosome interactions, 240, 247, 249 Human immunodeficiency virus (HIV), 375, 463, 467, 470 virus replication cycle, 462, 465 Human papillomavirus (HPV), 463 Hsp78, 373 Human parainfluenza virus (HPIV), 464 Hsp82, 322, 325 Human T-lymphotropic virus (HTLV), 467 Hsp90 Huntington’s disease (HD), 213, 450, 530 chemical biology HYOU1, 462 equilibrium and kinetic binding, 497–502 HypF-N, 222 essentiality studies, 502–505 historical perspective, 497 kinetic selectivity for cancer I diagnostics, 505–508 IAPP, 522 proteomics, 508–510 IKK, 467 prospects for study, 510–511 IMMP2, 158 clients IRE1 binding site, 335–336 BiP interactions, 68–69, 84–87 overview, 334 chaperone interactions, 69, 85–87 recognition and folding, 334–335 direct activation by unfolded proteins, 83–85 cochaperones, 330–334 HFS1 integrated response, 445–446 diseases membrane signaling, 63 cancer, 336–337 prospects for study, 70–71 cochaperones, 338 stress-sensing models, 63–68 neurodegenerative disease, 337 translation repression, 87–90 psychiatric disease, 337–338 translocon interactions and oligomerization, 69–70 endoplasmic reticulum–associated degradation, 130, unfolded 135 protein response-sensing overview, 60–63, 77, 484–485, 488 evolution and isoforms, 322–323 history of study, 321–322 inhibitors amino-terminal inhibitors, 338–339 J binding disruption, 339–340 Japanese encephalitis virus (JEV), 462–463, 470 carboxy-terminal inhibitors, 339 JEV.
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    JCB: Review Pathways of cellular proteostasis in aging and disease Courtney L. Klaips, Gopal Gunanathan Jayaraj, and F. Ulrich Hartl Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany Ensuring cellular protein homeostasis, or proteostasis, re- control of abundance and subcellular localization, and finally, quires precise control of protein synthesis, folding, confor- disposal by degradation. A complex proteostasis network (PN) acts at each of these mational maintenance, and degradation. A complex and steps to maintain a balanced proteome linked by molecular adaptive proteostasis network coordinates these processes chaperones of different classes as central players. These factors with molecular chaperones of different classes and their ensure de novo folding in a crowded cellular environment and regulators functioning as major players. This network maintain proteins in a soluble, nonaggregated state. Moreover, in conditions that disfavor folding or solubility, certain chaper- serves to ensure that cells have the proteins they need ones act to target misfolded proteins for degradation or spatial while minimizing misfolding or aggregation events that sequestration, thus protecting the rest of the proteome from ab- are hallmarks of age-associated proteinopathies, includ- errant interactions (Balchin et al., 2016; Sontag et al., 2017). Here, we describe the major pathways of cellular pro- ing neurodegenerative disorders such as Alzheimer’s and teostasis and outline the challenges they face during aging and Parkinson’s diseases. It is now clear that the capacity of disease. We exemplify these processes using mainly the proteo- cells to maintain proteostasis undergoes a decline during stasis pathways operating in the cytosol, where most cellular aging, rendering the organism susceptible to these pa- proteins are produced.
  • CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis—Literature Review and Case Report

    CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis—Literature Review and Case Report

    G C A T T A C G G C A T genes Article CLN8 Mutations Presenting with a Phenotypic Continuum of Neuronal Ceroid Lipofuscinosis—Literature Review and Case Report Magdalena Badura-Stronka 1,*,†, Anna Winczewska-Wiktor 2,†, Anna Pietrzak 3,†, Adam Sebastian Hirschfeld 1, Tomasz Zemojtel 4, Katarzyna Woły ´nska 1, Katarzyna Bednarek-Rajewska 5, Monika Seget-Dubaniewicz 5, Agnieszka Matheisel 6, Anna Latos-Bielenska 1 and Barbara Steinborn 2 1 Chair and Department of Medical Genetics, Poznan University of Medical Sciences, 60-352 Poznan, Poland; [email protected] (A.S.H.); [email protected] (K.W.); [email protected] (A.L.-B.) 2 Chair and Department of Developmental Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland; [email protected] (A.W.-W.); [email protected] (B.S.) 3 Department of Neurology, 10th Military Research Hospital and Polyclinic, 85-681 Bydgoszcz, Poland; [email protected] 4 BIH Genomics Core Unit, Campus Mitte, Charite University Medicine, 13353 Berlin, Germany; [email protected] 5 Department of Clinical Pathology, Poznan University of Medical Sciences, 60-355 Poznan, Poland; [email protected] (K.B.-R.); [email protected] (M.S.-D.) 6 Citation: Badura-Stronka, M.; Department of Developmental Neurology, Gdansk Medical University, 80-307 Gdansk, Poland; Winczewska-Wiktor, A.; Pietrzak, A.; [email protected] * Correspondence: [email protected] Hirschfeld, A.S.; Zemojtel, T.; † These authors contributed equally to this work. Woły´nska,K.; Bednarek-Rajewska, K.; Seget-Dubaniewicz, M.; Matheisel, A.; Latos-Bielenska, A.; Steinborn, B. Abstract: CLN8 is a ubiquitously expressed membrane-spanning protein that localizes primarily CLN8 Mutations Presenting with a in the ER, with partial localization in the ER-Golgi intermediate compartment.