The first report of direct inhibitors that target the C-terminal MEEVD region on heat shock protein 90

2016 ◽  
Vol 52 (3) ◽  
pp. 501-504 ◽  
Author(s):  
L. K. Buckton ◽  
H. Wahyudi ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
First Report ◽  
C Terminus ◽  
Direct Inhibitors

Inhibitors binding to the C-terminus of Hsp90 and blocking access to the TPR co-chaperones.

C-terminal heat shock protein 90 modulators produce desirable oncogenic properties

2015 ◽  
Vol 13 (16) ◽  
pp. 4627-4631 ◽  
Author(s):  
Y. Wang ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Cellular Protection ◽  
Protection Mechanism ◽  
C Terminus ◽  
N Terminus ◽  
Shock Response

The cellular protection mechanism, the heat shock response, is only activated by classical heat shock 90 inhibitors (Hsp90) that “target” the N-terminus of the protein, but not by those that modulate the C-terminus.

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.

Blocking the heat shock response and depleting HSF-1 levels through heat shock protein 90 (hsp90) inhibition: a significant advance on current hsp90 chemotherapies

RSC Advances ◽  
2015 ◽  
Vol 5 (73) ◽  
pp. 59003-59013 ◽  
Author(s):  
Yen Chin Koay ◽  
Jeanette R. McConnell ◽  
Yao Wang ◽  
Shelli R. McAlpine
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Heat Shock Protein 90 ◽  
Significant Advance ◽  
Hsp90 Inhibition ◽  
C Terminus ◽  
Shock Response

C-terminal inhibitors of heat shock protein 90 (hsp90) modulate the C-terminus and do not elicit a heat shock response.

Glycyrrhizin effects rat hepatocytes via the reduction of heat shock protein 90 expression

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Rat Hepatocytes
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