Abstract
In this chapter are presented chaperonopathies in which a genetic mechanism is involved but are different from those discussed in chapter 4. Thus, chaperonopathies due to gene dysregulation such as those observed in aged individuals and in some cases with neurodegenerative diseases (e.g., Alzheimer’s, Huntington’s, Parkinson’s, and other conditions), are presented. Likewise, examples of the impact of chaperone-gene polymorphisms on health and disease are given. The quantitative chaperonopathies attributable to gene dysregulation are discussed.
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Further Reading
Section 5.1 CHAPERONOPATHIES DUE TO GENE DYSREGULATION DnaJB
This gene is upregulated in Parkinsons disease. DNAJB6 is increased in astrocytes in Parkinson’s disease, and it is present in Lewy bodies. Durrenberger PF, Filiou MD, Moran LB, Michael GJ, Novoselov S, Cheetham ME, Clark P, Pearce RK, Graeber MB (2009). DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in parkinsonian astrocytes. J Neurosci Res 87:238–245
Grp78 (HSPA5)
This ER chaperone is increased in hereditary reducing-body myopathy (RBM). Liewluck T, Hayashi YK, Ohsawa M, Kurokawa R, Fujita M, Noguchi S, Nonaka I, Nishino I (2007) Unfolded protein response and aggresome formation in hereditary reducing-body myopathy. Muscle Nerve 35:322–326
AHSP (See also Further Reading for Sects. 2.1, 4.4 and 5.3)
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AlphaB-Crystallin (CRYAB; HspB5)
This small Hsp is overexpressed in some neurodegenerative disorders. This increase in HspB5 may be paralleled in familial amyloidotic polyneuropathy, which is characterized by deposition of mutated transthyretin in the extracellular space, by activation of the heat-shock factor HSF-1 and increase in Hsp27 and Hsp70. Magalhães J, Santos SD, Saraiva MJ (2010) AlphaB-crystallin (HspB5) in familial amyloidotic polyneuropathy. Int J Exp Pathol 91:515–521
Nopp140
Renvoisé B, Colasse S, Burlet P, Viollet L, Meier UT, Lefebvre S (2009) The loss of the snoRNP chaperone Nopp140 from Cajal bodies of patient fibroblasts correlates with the severity of spinal muscular atrophy. Hum Mol Genet 18:1181–1189
Chaperones in Brain Deficiency
Yoo BC, Fountoulakis M, Dierssen M, Lubec G (2001) Expression patterns of chaperone proteins in cerebral cortex of the fetus with Down syndrome: dysregulation of T-complex protein 1. J Neural Transm. Supplementum 61:321–324
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Section 5.2 HUMAN CHAPERONE-GENE POLYMORPHISMS
Polymorphisms of interest can occur in the promoter-regulatory or in the protein-coding regions of the chaperone genes themselves, or of the regulatory genes (e.g., HSF gene)
CRYAB (HspB5)
It was reported that the G allele of CRYAB C-802G correlated with oral cancer risk. Consequently, it was proposed that this polymorphism could be a useful marker to assess and predict oral cancer recurrence and patient survival
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Hsp70 FAMILY
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Karoly E, Fekete A, Banki NF, Szebeni B, Vannay A, Szabo AJ, Tulassay T, Reusz GS (2007) Heat shock protein 72 (HSPA1B) gene polymorphism and toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatr Res 61:371–374
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Other chaperones
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Jeng JE, Tsai JF, Chuang LY, Ho MS, Lin ZY, Hsieh MY, Chen SC, Chuang WL, Wang LY, Yu ML, Dai CY, Chang JG (2008) Heat shock protein A1B 1267 polymorphism is highly associated with risk and prognosis of hepatocellular carcinoma: a case-control study. Medicine (Baltimore) 87:87–98
Lu J, Hu Z, Wei S, Wang LE, Liu Z, El-Naggar AK, Sturgis EM, Wei Q (2009) A novel functional variant (−842G > C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity. Carcinogenesis 30:1717–1721
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Section 5.3 Chaperonopathies due to Substrate Mutation that Interferes with the Chaperone-Substrate Interaction
Altschuler GM, Dekker C, McCormack EA, Morris EP, Klug DR, Willison KR (2009) A single amino acid residue is responsible for species-specific incompatibility between CCT and alpha-actin. FEBS Lett 583:782–786
Feldman DE, Thulasiraman V, Ferreyra RG, Frydman J (1999) Formation of the VHL-elongin BC tumor suppressor complex is mediated by the chaperonin TRiC. Mol Cell 4:1051–1061
Hutt DM, Martino Roth D, Chalfant M, Youker RT, Matteson J, Brodsky JL, Balch WE (2012) FKBP8 Peptidyl-Prolyl-isomerase activity manages a late stage of CFTR folding and stability. J Biol Chem 287:21914–21925
Moreau KL, King JA (2012) Cataract-causing defect of a mutant γ-Crystallin proceeds through an aggregation pathway which bypasses recognition by the α-Crystallin chaperone. PLoS ONE. 7(5):e37256
Rosser MF, Grove DE, Chen L, Cyr DM (2008) Assembly and misassembly of CFTR: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of MSD1 and MSD2. Mol Biol Cell 19:4570–4279
Saxena A, Banasavadi-Siddegowda YK, Fan Y, Bhattacharya S, Roy G, Giovannucci DR, Frizzell RA, Wang X (2012) Human heat shock protein 105/110 kDa (Hsp105/110) regulates biogenesis and quality control of misfolded cystic fibrosis transmembrane conductance regulator at multiple levels. J Biol Chem 287:19158–19170
Sims KB (2001) Von Hippel-Lindau disease: gene to bedside. Curr Opin Neurol 14:695–703
Speisky D, Duces A, Bieche I, Rebours V, Hammel P, Sauvanet A, Richard S, Bedossa P, Vidaud M, Murat A, Niccoli P, Scoazec JY, Ruszniewski P, Couvelard A (2012) Molecular profiling of pancreatic neuroendocrine tumors in sporadic and von Hippel-Lindau patients. Clin Cancer Res 18:2838–2849
Tian G, Kong XP, Jaglin XH, Chelly J, Keays D, Cowan NJ (2008) A pachygyria-causing alpha-tubulin mutation results in inefficient cycling with CCT and a deficient interaction with TBCB. Mol Biol Cell 19:1152–1161
Wang Y, Tian G, Cowan NJ, Cabral F (2006) Mutations affecting beta-tubulin folding and degradation. J Biol Chem 281:13628–13635
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Macario, A.J., Conway de Macario, E., Cappello, F. (2013). Other Genetic Chaperonopathies. In: The Chaperonopathies. SpringerBriefs in Biochemistry and Molecular Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4667-1_5
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DOI: https://doi.org/10.1007/978-94-007-4667-1_5
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