Hsp70 clears misfolded kinases that partitioned into distinct quality-control compartments

Molecular Biology of the Cell
Joydeep RoyAtin K Mandal

Abstract

Hsp70 aids in protein folding and directs misfolded proteins to the cellular degradation machinery. We describe discrete roles of Hsp70,SSA1 as an important quality-control machinery that switches functions to ameliorate the cellular environment. SSA1 facilitates folding/maturation of newly synthesized protein kinases by aiding their phosphorylation process and also stimulates ubiquitylation and degradation of kinases in regular protein turnover or during stress when kinases are denatured or improperly folded. Significantly, while kinases accumulate as insoluble inclusions upon SSA1 inhibition, they form soluble inclusions upon Hsp90 inhibition or stress foci during heat stress. This suggests formation of inclusion-specific quality-control compartments under various stress conditions. Up-regulation of SSA1 results in complete removal of these inclusions by the proteasome. Elevation of the cellular SSA1 level accelerates kinase turnover and protects cells from proteotoxic stress. Upon overexpression, SSA1 targets heat-denatured kinases toward degradation, which could enable them to recover their functional state under physiological conditions. Thus active participation of SSA1 in the degradation of misfolded proteins establishes...Continue Reading

References

Oct 9, 1975·Biochimica Et Biophysica Acta·M M GrantC Franzblau
Jul 1, 1987·Molecular and Cellular Biology·M Werner-WashburneE A Craig
Feb 26, 1998·Cell·B Bukau, A L Horwich
Feb 14, 2004·Human Molecular Genetics·Leonard PetrucelliMike Hutton
Aug 11, 2004·The Journal of Biological Chemistry·Szymon ZietkiewiczKrzysztof Liberek
Oct 1, 2004·Molecular and Cellular Biology·Zhong HuangXiao-Hong Sun
Mar 17, 2005·Cellular and Molecular Life Sciences : CMLS·M P Mayer, B Bukau
Oct 7, 2005·Molecular Biology of the Cell·Verena ArndtJörg Höhfeld
Oct 14, 2005·The Journal of Biological Chemistry·Lance ShanerKevin A Morano
Jul 21, 2006·The Journal of Biological Chemistry·Nela S Cintron, David Toft
Nov 9, 2006·The Journal of Biological Chemistry·Eman BashaElizabeth Vierling
Dec 23, 2006·Trends in Cell Biology·Avrom J CaplanMaria A Theodoraki
Jul 17, 2007·Trends in Biochemical Sciences·Pierre Goloubinoff, Paolo De Los Rios
Apr 30, 2008·Molecular and Cellular Biology·Atin K MandalAvrom J Caplan
May 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Peter M DouglasDouglas M Cyr
Aug 30, 2008·Nature·Daniel KaganovichJudith Frydman
Oct 3, 2008·Molecular Biology of the Cell·Gary A FlomJill L Johnson
Oct 15, 2008·Journal of Molecular Endocrinology·Eirini MeimaridouJ Paul Chapple
Oct 16, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yan WangMichael Y Sherman
Jun 13, 2009·Protein and Peptide Letters·Deepak Sharma, Daniel C Masison
Jun 27, 2009·Prion·Daniel C MasisonDeepak Sharma
Oct 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Umesh K JinwalChad A Dickey
Oct 13, 2009·Molecular Cell·J I-Ju LeuDonna L George
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jarrod W HeckRandolph Y Hampton
Mar 20, 2010·Molecular Biology of the Cell·Atin K MandalKevin A Morano
Mar 24, 2010·The Journal of Biological Chemistry·Umesh K JinwalChad A Dickey
May 14, 2010·Molecular Biology of the Cell·Rupali PrasadDavis T W Ng
May 14, 2010·Molecular Biology of the Cell·Nadinath B NillegodaAvrom J Caplan
Jul 24, 2010·Nature Reviews. Molecular Cell Biology·Harm H Kampinga, Elizabeth A Craig
Aug 14, 2010·Molecular Cell·Matthias P Mayer

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Citations

May 1, 2017·Parasitology International·Ananya JanaSrimonti Sarkar
Oct 21, 2016·The Journal of Biological Chemistry·Shahana MitraAtin K Mandal

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Methods Mentioned

BETA
protein folding
nucleotide exchange
ubiquitination
immunoprecipitation
fluorescence microscopy
electrophoresis
pull-down
protein kinase assay
PCR
confocal microscopy

Software Mentioned

ImageJ

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