scholarly journals Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation

Biochemistry ◽  
2015 ◽  
Vol 54 (48) ◽  
pp. 7120-7131 ◽  
Author(s):  
Victoria A. Assimon ◽  
Daniel R. Southworth ◽  
Jason E. Gestwicki
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Specific Binding ◽  
Heat Shock Protein 90 ◽  
Tetratricopeptide Repeat ◽  
Repeat Proteins ◽  
Tetratricopeptide Repeat Proteins

scholarly journals Cell Surface-bound Heat Shock Protein 70 (Hsp70) Mediates Perforin-independent Apoptosis by Specific Binding and Uptake of Granzyme B

2003 ◽  
Vol 278 (42) ◽  
pp. 41173-41181 ◽  
Author(s):  
Catharina Gross ◽  
Walter Koelch ◽  
Antonio DeMaio ◽  
Nelson Arispe ◽  
Gabriele Multhoff
Keyword(s):  
Heat Shock ◽  
Cell Surface ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Specific Binding ◽  
Granzyme B

scholarly journals C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins

2009 ◽  
Vol 423 (3) ◽  
pp. 411-419 ◽  
Author(s):  
Andrew J. Ramsey ◽  
Lance C. Russell ◽  
Michael Chinkers
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Homo Sapiens ◽  
Heat Shock Protein 90 ◽  
Phage Library ◽  
Tetratricopeptide Repeat ◽  
Terminal Sequence ◽  
C Terminus ◽  
Multiple Copies ◽  
Shock Proteins

Steroid-hormone-receptor maturation is a multi-step process that involves several TPR (tetratricopeptide repeat) proteins that bind to the maturation complex via the C-termini of hsp70 (heat-shock protein 70) and hsp90 (heat-shock protein 90). We produced a random T7 peptide library to investigate the roles played by the C-termini of the two heat-shock proteins in the TPR–hsp interactions. Surprisingly, phages with the MEEVD sequence, found at the C-terminus of hsp90, were not recovered from our biopanning experiments. However, two groups of phages were isolated that bound relatively tightly to HsPP5 (Homo sapiens protein phosphatase 5) TPR. Multiple copies of phages with a C-terminal sequence of LFG were isolated. These phages bound specifically to the TPR domain of HsPP5, although mutation studies produced no evidence that they bound to the domain's hsp90-binding groove. However, the most abundant family obtained in the initial screen had an aspartate residue at the C-terminus. Two members of this family with a C-terminal sequence of VD appeared to bind with approximately the same affinity as the hsp90 C-12 control. A second generation pseudo-random phage library produced a large number of phages with an LD C-terminus. These sequences acted as hsp70 analogues and had relatively low affinities for hsp90-specific TPR domains. Unfortunately, we failed to identify residues near hsp90's C-terminus that impart binding specificity to individual hsp90–TPR interactions. The results suggest that the C-terminal sequences of hsp70 and hsp90 act primarily as non-specific anchors for TPR proteins.

Inhibition of heat shock protein 70 blocks the development of cardiac hypertrophy by modulating the phosphorylation of histone deacetylase 2

2018 ◽  
Vol 115 (13) ◽  
pp. 1850-1860 ◽  
Author(s):  
Somy Yoon ◽  
Mira Kim ◽  
Hyun-Ki Min ◽  
Yeong-Un Lee ◽  
Duk-Hwa Kwon ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cardiac Hypertrophy ◽  
Histone Deacetylase ◽  
Heat Shock Protein 70 ◽  
Specific Binding ◽  
Primary Cultures ◽  
Histone Deacetylase 2 ◽  
Ventricular Cardiomyocytes

Abstract Aims Previously, we reported that phosphorylation of histone deacetylase 2 (HDAC2) and the resulting activation causes cardiac hypertrophy. Through further study of the specific binding partners of phosphorylated HDAC2 and their mechanism of regulation, we can better understand how cardiac hypertrophy develops. Thus, in the present study, we aimed to elucidate the function of one such binding partner, heat shock protein 70 (HSP70). Methods and results Primary cultures of rat neonatal ventricular cardiomyocytes and H9c2 cardiomyoblasts were used for in vitro cellular experiments. HSP70 knockout (KO) mice and transgenic (Tg) mice that overexpress HSP70 in the heart were used for in vivo analysis. Peptide-precipitation and immunoprecipitation assay revealed that HSP70 preferentially binds to phosphorylated HDAC2 S394. Forced expression of HSP70 increased phosphorylation of HDAC2 S394 and its activation, but not that of S422/424, whereas knocking down of HSP70 reduced it. However, HSP70 failed to phosphorylate HDAC2 in the cell-free condition. Phosphorylation of HDAC2 S394 by casein kinase 2α1 enhanced the binding of HSP70 to HDAC2, whereas dephosphorylation induced by the catalytic subunit of protein phosphatase 2A (PP2CA) had the opposite effect. HSP70 prevented HDAC2 dephosphorylation by reducing the binding of HDAC2 to PP2CA. HSP70 KO mouse hearts failed to phosphorylate S394 HDAC2 in response to isoproterenol infusion, whereas Tg overexpression of HSP70 increased the phosphorylation and activation of HDAC2. 2-Phenylethynesulfonamide (PES), an HSP70 inhibitor, attenuated cardiac hypertrophy induced either by phenylephrine in neonatal ventricular cardiomyocytes or by aortic banding in mice. PES reduced HDAC2 S394 phosphorylation and its activation by interfering with the binding of HSP70 to HDAC2. Conclusion These results demonstrate that HSP70 specifically binds to S394-phosphorylated HDAC2 and maintains its phosphorylation status, which results in HDAC2 activation and the development of cardiac hypertrophy. Inhibition of HSP70 has possible application as a therapeutic.

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