Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90

Sager, Rebecca; Woodford, Mark R.; Backe, Sarah J.; Makedon, Alan M.; Baker-Williams, Alexander J.; DiGregorio, Bryanna T.; Loiselle, David R.; Haystead, Timothy; Zachara, Natasha E.; Prodromou, Chrisostomos; Bourboulia, Dimitra; Schmidt, Laura S.; Linehan, W. Marston; Bratslavsky, Gennady; Mollapour, Mehdi

doi:10.1016/j.celrep.2019.01.018

Cited by 37 publications

(36 citation statements)

References 50 publications

(78 reference statements)

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“…Phosphorylation can be added and removed rapidly, allowing fine-tuning chaperone function when required. The large number of detected phosphorylations suggest a "chaperone code" similar in nature to the combinatory PTM code that exists on histones (Nitika and Truman 2017;Cloutier and Coulombe 2013;Sager et al 2018Sager et al , 2019Mollapour and Neckers 2012). Several regulatory phosphorylation sites have been detected on Hsp70 in human cells; these include T38, T66, T495, T504 and T636 which control cell cycle progression, condensation of chromosomes, translational inhibition, Hsp70 dimerization and client triaging, respectively (Nitika and Truman 2017).…”

Section: Specific Post-translational Modification Of Hsp70 Isoformsmentioning

confidence: 97%

Not quite the SSAme: unique roles for the yeast cytosolic Hsp70s

et al. 2019

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The Heat Shock Protein 70s (Hsp70s) are an essential family of proteins involved in folding of new proteins and triaging of damaged proteins for proteasomal-mediated degradation. They are highly conserved in all organisms, with each organism possessing multiple highly similar Hsp70 variants (isoforms). These isoforms have been previously thought to be identical in function differing only in their spatio-temporal expression pattern. The model organism Saccharomyces cerevisiae (baker's yeast) expresses four Hsp70 isoforms Ssa1, 2, 3 and 4. Here, we review recent findings that suggest that despite their similarity, Ssa isoforms may have unique cellular functions.

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Section: Specific Post-translational Modification Of Hsp70 Isoformsmentioning

confidence: 97%

Not quite the SSAme: unique roles for the yeast cytosolic Hsp70s

et al. 2019

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“…As the resolution of proteomic technologies improves, we may thus find that Hsp70s are modified with many more PTMs than currently known. Studies of individual sites are still nontrivial, especially given the complex reciprocal relationship between chaperones and those clients that are able to modify chaperones and that choice of expression host dictates PTMs added to Hsp70 when made recombinantly (57,188,189).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

Nitika

Porter

Truman

et al. 2020

Journal of Biological Chemistry

109

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Cells must be able to cope with the challenge of folding newly synthesized proteins and refolding those that have become misfolded in the context of a crowded cytosol. One such coping mechanism that has appeared during evolution is the expression of well-conserved molecular chaperones, such as those that are part of the heat shock protein 70 (Hsp70) family of proteins that bind and fold a large proportion of the proteome. Although Hsp70 family chaperones have been extensively examined for the last 50 years, most studies have focused on regulation of Hsp70 activities by altered transcription, co-chaperone “helper” proteins, and ATP binding and hydrolysis. The rise of modern proteomics has uncovered a vast array of post-translational modifications (PTMs) on Hsp70 family proteins that include phosphorylation, acetylation, ubiquitination, AMPylation, and ADP-ribosylation. Similarly to the pattern of histone modifications, the histone code, this complex pattern of chaperone PTMs is now known as the “Chaperone Code.” In this review, we discuss the history of the Hsp70 chaperone code, its currently understood regulation and functions, as well as thoughts on what the future of research into the chaperone code may entail.

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“…There is growing evidence that a range of post-translational modifications (PTMs) such as phosphorylation, acetylation, methylation, ubiquitination, and SUMOylation all play a role in the activity, and specificity of chaperones and co-chaperones (Cloutier and Coulombe, 2013; Mollapour et al, 2014; Nitika and Truman, 2017; Sager et al, 2019). Tyrosine phosphorylation of Hsp70 regulates both its activity and translocation to the nucleus (Knowlton et al, 2000).…”

Section: Regulatory Mechanisms That Control Formation Of Hsp70 Oligommentioning

confidence: 99%

Oligomerization of Hsp70: Current Perspectives on Regulation and Function

Takakuwa

Nitika

Knighton

et al. 2019

Front. Mol. Biosci.

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The Hsp70 molecular chaperone in conjunction with Hsp90 and a suite of helper co-chaperones are required for the folding and subsequent refolding of a large proportion of the proteome. These proteins are critical for cell viability and play major roles in diseases of proteostasis which include neurodegenerative diseases and cancer. As a consequence, a large scientific effort has gone into understanding how chaperones such as Hsp70 function at the in vitro and in vivo level. Although many chaperones require constitutive self-interaction (dimerization and oligomerization) to function, Hsp70 has been thought to exist as a monomer, especially in eukaryotic cells. Recent studies have demonstrated that both bacterial and mammalian Hsp70 can exist as a dynamic pool of monomers, dimer, and oligomers. In this mini-review, we discuss the mechanisms and roles of Hsp70 oligomerization in Hsp70 function, as well as thoughts on how this integrates into well-established ideas of Hsp70 regulation.

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Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90

Cited by 37 publications

References 50 publications

Not quite the SSAme: unique roles for the yeast cytosolic Hsp70s

Not quite the SSAme: unique roles for the yeast cytosolic Hsp70s

Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

Oligomerization of Hsp70: Current Perspectives on Regulation and Function

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