Genomes and Genes
alpha crystallin b chain
Summary: One of the alpha crystallin subunits. In addition to being expressed in the lens (LENS, CRYSTALLINE), alpha-crystallin B chain has been found in a variety of tissues such as HEART; BRAIN; MUSCLE; and KIDNEY. Accumulation of the protein in the brain is associated with NEURODEGENERATIVE DISEASES such as CREUTZFELDT-JAKOB SYNDROME and ALEXANDER DISEASE.
- Morozov V, Wawrousek E. Caspase-dependent secondary lens fiber cell disintegration in alphaA-/alphaB-crystallin double-knockout mice. Development. 2006;133:813-21 pubmed
- Ecroyd H, Meehan S, Horwitz J, Aquilina J, Benesch J, Robinson C, et al. Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochem J. 2007;401:129-41 pubmed
- Narayanan S, Kamps B, Boelens W, Reif B. alphaB-crystallin competes with Alzheimer's disease beta-amyloid peptide for peptide-peptide interactions and induces oxidation of Abeta-Met35. FEBS Lett. 2006;580:5941-6 pubmed..J. et al. (1999) The molecular chaperone alphaB-crystallin enhances amyloid-beta neurotoxicity. Biochem. Biophys. Res. Commun. 262, 152-156.]. ..
- Nakata K, Crabb J, Hollyfield J. Crystallin distribution in Bruch's membrane-choroid complex from AMD and age-matched donor eyes. Exp Eye Res. 2005;80:821-6 pubmed..These findings suggest that the accumulation of these small heat shock proteins at this critical interface below the RPE reflects a disease-related stress response manifested during the progression of AMD...
- Swaim C, Smith D, Smith J. The reaction of alpha-crystallin with the cross-linker 3,3'-dithiobis(sulfosuccinimidyl propionate) demonstrates close proximity of the C termini of alphaA and alphaB in the native assembly. Protein Sci. 2004;13:2832-5 pubmed..This cross-link provides experimental evidence supporting theoretical structural models that place the C termini of alphaA and alphaB within close proximity in the native aggregate. ..
- Liu S, Li J, Tao Y, Xiao X. Small heat shock protein alphaB-crystallin binds to p53 to sequester its translocation to mitochondria during hydrogen peroxide-induced apoptosis. Biochem Biophys Res Commun. 2007;354:109-14 pubmed..Hence, this study provides a hint that alphaB-crystallin affects on p53 mitochondrial translocation during oxidative stress-induced apoptosis. ..
- Jehle S, van Rossum B, Stout J, Noguchi S, Falber K, Rehbein K, et al. alphaB-crystallin: a hybrid solid-state/solution-state NMR investigation reveals structural aspects of the heterogeneous oligomer. J Mol Biol. 2009;385:1481-97 pubmed publisher..8. This steep pH-dependent switch may be important for alphaB to function optimally (e.g., to preserve the filament integrity of cardiac muscle proteins such as actin and desmin during cardiac ischemia, which is accompanied by acidosis). ..
- Chávez Zobel A, Loranger A, Marceau N, Theriault J, Lambert H, Landry J. Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. Hum Mol Genet. 2003;12:1609-20 pubmed
- Gupta R, Srivastava O. Effect of deamidation of asparagine 146 on functional and structural properties of human lens alphaB-crystallin. Invest Ophthalmol Vis Sci. 2004;45:206-14 pubmed..The results show that the deamidation of N146 but not of N78 have profound effects on the structural and functional properties of alphaB-crystallin. ..
- Murugesan R, Santhoshkumar P, Sharma K. Role of alphaBI5 and alphaBT162 residues in subunit interaction during oligomerization of alphaB-crystallin. Mol Vis. 2008;14:1835-44 pubmed
- Rekas A, Adda C, Andrew Aquilina J, Barnham K, Sunde M, Galatis D, et al. Interaction of the molecular chaperone alphaB-crystallin with alpha-synuclein: effects on amyloid fibril formation and chaperone activity. J Mol Biol. 2004;340:1167-83 pubmed..In summary, alpha-synuclein and alphaB-crystallin interact readily with each other and affect each other's properties, in particular alpha-synuclein fibril formation and alphaB-crystallin chaperone action. ..
- Ghosh J, Estrada M, Clark J. Structure-based analysis of the beta8 interactive sequence of human alphaB crystallin. Biochemistry. 2006;45:9878-86 pubmed..The results established the beta3-beta8-beta9 surface of the alpha crystallin core domain as an interface for complex assembly and chaperone activity. ..
- Bhattacharyya J, Padmanabha Udupa E, Wang J, Sharma K. Mini-alphaB-crystallin: a functional element of alphaB-crystallin with chaperone-like activity. Biochemistry. 2006;45:3069-76 pubmed..Kynurenine modification of His in the peptide abolishes the antiaggregation property of the mini-chaperone. These data suggest that the 73-92 region in alphaB-crystallin is one of the substrate binding sites during chaperone activity. ..
- Minami M, Mizutani T, Kawanishi R, Suzuki Y, Mori H. Neuronal expression of alphaB crystallin in cerebral infarction. Acta Neuropathol. 2003;105:549-54 pubmed
- Liu L, Ghosh J, Clark J, Jiang S. Studies of alphaB crystallin subunit dynamics by surface plasmon resonance. Anal Biochem. 2006;350:186-95 pubmed
- Gruvberger Saal S, Parsons R. Is the small heat shock protein alphaB-crystallin an oncogene?. J Clin Invest. 2006;116:30-2 pubmed
- Thedieck C, Kalbacher H, Kratzer U, Lammers R, Stevanovic S, Klein G. alpha B-crystallin is a cytoplasmic interaction partner of the kidney-specific cadherin-16. J Mol Biol. 2008;378:145-53 pubmed publisher..These findings suggest that the interaction of Ksp-cadherin with alpha B-crystallin is important for the connection of Ksp-cadherin to the cytoskeleton and thus for maintaining tissue integrity in the kidney. ..
- Li H, Li C, Lu Q, Su T, Ke T, Li D, et al. Cataract mutation P20S of alphaB-crystallin impairs chaperone activity of alphaA-crystallin and induces apoptosis of human lens epithelial cells. Biochim Biophys Acta. 2008;1782:303-9 pubmed publisher..These results suggest that the changes in the structure and function of the alpha-crystallin complex and cytotoxicity are vital factors in the pathogenesis of congenital cataract linked to the P20S mutation in the alphaB-crystallin. ..
- Gangalum R, Schibler M, Bhat S. Small heat shock protein alphaB-crystallin is part of cell cycle-dependent Golgi reorganization. J Biol Chem. 2004;279:43374-7 pubmed
- Ghosh J, Houck S, Clark J. Interactive sequences in the molecular chaperone, human alphaB crystallin modulate the fibrillation of amyloidogenic proteins. Int J Biochem Cell Biol. 2008;40:954-67 pubmed..This is the first characterization of specific bioactive peptides synthesized on the basis of interactive domains in the small heat shock protein, alphaB crystallin that protect against the fibrillation of amyloidogenic proteins. ..
- Singh B, Rao K, Ramakrishna T, Rangaraj N, Rao C. Association of alphaB-crystallin, a small heat shock protein, with actin: role in modulating actin filament dynamics in vivo. J Mol Biol. 2007;366:756-67 pubmed..Further, our studies suggest that the association of alphaB-crystallin with actin helps maintenance of pinocytosis, a physiological function essential for survival of cells. ..
- Gupta R, Srivastava O. Deamidation affects structural and functional properties of human alphaA-crystallin and its oligomerization with alphaB-crystallin. J Biol Chem. 2004;279:44258-69 pubmed
- Chen L, Holland G, Yu F, Levinson R, Lampi K, Horwitz J, et al. Associations of seroreactivity against crystallin proteins with disease activity and cataract in patients with uveitis. Invest Ophthalmol Vis Sci. 2008;49:4476-81 pubmed publisher..The relationship between the presence of specific anti-crystallin antibodies and active inflammation may indicate a role for these autoantibodies in uveitis pathogenesis. ..
- Santhoshkumar P, Sharma K. Conserved F84 and P86 residues in alphaB-crystallin are essential to effectively prevent the aggregation of substrate proteins. Protein Sci. 2006;15:2488-98 pubmed..This study further supports the involvement of the residues in the 73-92 region of alphaB-crystallin in substrate protein binding and chaperone-like action. ..
- Lin D, Barbash O, Kumar K, Weber J, Harper J, Klein Szanto A, et al. Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell. 2006;24:355-66 pubmed..We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. ..
- Ghosh J, Houck S, Clark J. Interactive sequences in the stress protein and molecular chaperone human alphaB crystallin recognize and modulate the assembly of filaments. Int J Biochem Cell Biol. 2007;39:1804-15 pubmed publisher..The results support the hypothesis that interactive domains in alphaB crystallin have multiple functions in stabilizing the cytoskeleton and protecting cytosolic proteins from unfolding...
- Yang J, Luo L, Liu X, Rosenblatt M, Qu B, Liu Y, et al. Down regulation of the PEDF gene in human lens epithelium cells changed the expression of proteins vimentin and alphaB-crystallin. Mol Vis. 2010;16:105-12 pubmed..To study the relationship of pigment epithelium-derived factor (PEDF) expression with the expression of vimentin and alphaB-crystallin by lens epithelial cells...
- Liu Y, Zhang X, Luo L, Wu M, Zeng R, Cheng G, et al. A novel alphaB-crystallin mutation associated with autosomal dominant congenital lamellar cataract. Invest Ophthalmol Vis Sci. 2006;47:1069-75 pubmed..These data indicate that the altered tertiary and/or quaternary structures and the dominant negative effect of D140N mutant alphaB-crystallin underlie the molecular mechanism of cataractogenesis of this pedigree. ..
- Ghosh J, Estrada M, Clark J. Interactive domains for chaperone activity in the small heat shock protein, human alphaB crystallin. Biochemistry. 2005;44:14854-69 pubmed..The results suggested that interactive sequences in human alphaB crystallin have dual roles in subunit-subunit assembly and chaperone activity. ..
- Srivastava O, Srivastava K. Existence of deamidated alphaB-crystallin fragments in normal and cataractous human lenses. Mol Vis. 2003;9:110-8 pubmed..The results show that the N146 residue in human alphaB-crystallin undergoes in vivo deamidation and several fragments containing this modification exist in both WS and WI protein fractions of normal and cataractous human lenses. ..
- Fujita Y, Ohto E, Katayama E, Atomi Y. alphaB-Crystallin-coated MAP microtubule resists nocodazole and calcium-induced disassembly. J Cell Sci. 2004;117:1719-26 pubmed..Taken together, these results suggest that one of the functions of alphaB-crystallin is to bind MTs via MAP(s) and to give the MTs resistance to disassembly. ..
- Mao Y, Liu J, Xiang H, Li D. Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 2004;11:512-26 pubmed..Thus, our results demonstrate a novel antiapoptotic mechanism for alpha-crystallins. ..
- Liu M, Ke T, Wang Z, Yang Q, Chang W, Jiang F, et al. Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. Invest Ophthalmol Vis Sci. 2006;47:3461-6 pubmed..This study identified a second novel mutation in CRYAB in a large Chinese cataract family. Together, these results provide strong evidence that CRYAB is a pathogenic gene for congenital cataract. ..
- Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, Imahashi K, et al. Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation. 2005;112:3451-61 pubmed
- Raman B, Ban T, Sakai M, Pasta S, Ramakrishna T, Naiki H, et al. AlphaB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid beta-peptide and beta2-microglobulin. Biochem J. 2005;392:573-81 pubmed..Our study sheds light on the role of small heat-shock proteins in protein conformational diseases, particularly in Alzheimer's disease. ..
- Pilotto A, Marziliano N, Pasotti M, Grasso M, Costante A, Arbustini E. alphaB-crystallin mutation in dilated cardiomyopathies: low prevalence in a consecutive series of 200 unrelated probands. Biochem Biophys Res Commun. 2006;346:1115-7 pubmed
- Alge C, Priglinger S, Neubauer A, Kampik A, Zillig M, Bloemendal H, et al. Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin. Invest Ophthalmol Vis Sci. 2002;43:3575-82 pubmed..Overexpression of alphaB-crystallin may be an important mechanism for the RPE to prevent apoptotic cell death in response to cellular stress. ..
- Aquilina J, Benesch J, Ding L, Yaron O, Horwitz J, Robinson C. Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure. J Biol Chem. 2004;279:28675-80 pubmed
- Kamradt M, Chen F, Sam S, Cryns V. The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem. 2002;277:38731-6 pubmed..Taken together, our findings indicate that alpha B-crystallin is a novel negative regulator of myogenic apoptosis that directly links the differentiation program to apoptosis resistance. ..
- Wang X, Klevitsky R, Huang W, Glasford J, Li F, Robbins J. AlphaB-crystallin modulates protein aggregation of abnormal desmin. Circ Res. 2003;93:998-1005 pubmed..Significantly less aberrant desmin aggregation was observed in the WT-CryAB-overexpressing cells than in the HEK cells. The results suggest that CryAB modulates abnormal desmin aggregation and can serve a cardioprotective role. ..
- Goldfarb L, Vicart P, Goebel H, Dalakas M. Desmin myopathy. Brain. 2004;127:723-34 pubmed..Better understanding of disease pathogenesis would stimulate research focused on developing specific treatments for these conditions. ..
- Hayes V, Devlin G, Quinlan R. Truncation of alphaB-crystallin by the myopathy-causing Q151X mutation significantly destabilizes the protein leading to aggregate formation in transfected cells. J Biol Chem. 2008;283:10500-12 pubmed publisher..In support of this hypothesis, we show that Q151X alphaB-crystallin is found mainly in the insoluble fraction of cell extracts from transient transfected cells, due to the formation of cytoplasmic aggregates. ..
- Rekas A, Jankova L, Thorn D, Cappai R, Carver J. Monitoring the prevention of amyloid fibril formation by alpha-crystallin. Temperature dependence and the nature of the aggregating species. FEBS J. 2007;274:6290-304 pubmed..It was shown that alphaB-crystallin interrupted alpha-synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures. ..
- Yaung J, Jin M, Barron E, Spee C, Wawrousek E, Kannan R, et al. alpha-Crystallin distribution in retinal pigment epithelium and effect of gene knockouts on sensitivity to oxidative stress. Mol Vis. 2007;13:566-77 pubmed..Lack of alpha-crystallins renders RPE cells more susceptible to apoptosis from oxidative stress. Mitochondrial alpha-crystallins may play an important role in the protection from increased susceptibility of RPE in oxidative stress. ..
- Harrington V, McCall S, Huynh S, Srivastava K, Srivastava O. Crystallins in water soluble-high molecular weight protein fractions and water insoluble protein fractions in aging and cataractous human lenses. Mol Vis. 2004;10:476-89 pubmed..Further, the crystallin species of cataractous lenses showed increased truncation, deamidation of Asn to Asp residues, and oxidation of Trp residue. ..
- Ghosh J, Clark J. Insights into the domains required for dimerization and assembly of human alphaB crystallin. Protein Sci. 2005;14:684-95 pubmed..The subunit-subunit interaction sites formed a pattern of hydrophobic patches on the 3D surface of human alphaB crystallin. ..
- Whiston E, Sugi N, Kamradt M, Sack C, Heimer S, Engelbert M, et al. alphaB-crystallin protects retinal tissue during Staphylococcus aureus-induced endophthalmitis. Infect Immun. 2008;76:1781-90 pubmed publisher..We conclude that alphaB-crystallin is important in protecting sensitive retinal tissue during destructive inflammation that occurs during bacterial endophthalmitis. ..
- Selcen D, Engel A. Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann Neurol. 2003;54:804-10 pubmed
- Aggeli I, Beis I, Gaitanaki C. Oxidative stress and calpain inhibition induce alpha B-crystallin phosphorylation via p38-MAPK and calcium signalling pathways in H9c2 cells. Cell Signal. 2008;20:1292-302 pubmed publisher..Collectively, our findings underline alphaB-crystallin crucial role as a participant of cardiac cells early response to stressful stimuli compromising their survival. ..
- van Rijk A, Stege G, Bennink E, May A, Bloemendal H. Nuclear staining for the small heat shock protein alphaB-crystallin colocalizes with splicing factor SC35. Eur J Cell Biol. 2003;82:361-8 pubmed..Double staining experiments revealed colocalization of alphaB-crystallin with the splicing factor SC35 in nuclear speckles, suggesting a role for alphaB-crystallin in splicing or protection of the splicing machinery. ..
- Liao J, Lee J, Wu S, Chiou S. COOH-terminal truncations and site-directed mutations enhance thermostability and chaperone-like activity of porcine alphaB-crystallin. Mol Vis. 2009;15:1429-44 pubmed..Our study clearly demonstrated that both the length and electrostatic charge of the COOH-terminal segment play crucial roles in governing the structural stability and chaperone activity of alphaB-crystallin. ..
- Li D, Liu J, Mao Y, Xiang H, Wang J, Ma W, et al. Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by alpha B-crystallin through inhibition of RAS activation. Mol Biol Cell. 2005;16:4437-53 pubmed..Together, our results provide 1) a partial explanation for the lack of spontaneous tumor in the lens, 2) a novel signaling pathway for calcium-induced apoptosis, and 3) a novel antiapoptotic mechanism for alphaB-crystallin. ..