Open AccessThe 90-kDa Heat Shock Protein Stabilizes the Polysomal Ribonuclease 1 mRNA Endonuclease to Degradation by the 26S Proteasome
Author(s) -
Yong Peng,
Xiaoqiang Liu,
Daniel R. Schoenberg
Publication year - 2008
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e07-08-0774
Subject(s) - geldanamycin , biology , polysome , ribonuclease , hsp90 , phosphorylation , endonuclease , heat shock protein , proteasome , messenger rna , microbiology and biotechnology , biochemistry , enzyme , rna , ribosome , gene
The polysomal ribonuclease 1 (PMR1) mRNA endonuclease forms a selective complex with its translating substrate mRNAs where it is activated to initiate mRNA decay. Previous work showed tyrosine phosphorylation is required for PMR1 targeting to this polysome-bound complex, and it identified c-Src as the responsible kinase. c-Src phosphorylation occurs in a distinct complex, and the current study shows that 90-kDa heat shock protein (Hsp90) is also recovered with PMR1 and c-Src. Hsp90 binding to PMR1 is inhibited by geldanamycin, and geldanamycin stabilizes substrate mRNA to PMR1-mediated decay. PMR1 is inherently unstable and geldanamycin causes PMR1 to rapidly disappear in a process that is catalyzed by the 26S proteasome. We present a model where Hsp90 interacts transiently to stabilize PMR1 in a manner similar to its interaction with c-Src, thus facilitating the tyrosine phosphorylation and targeting of PMR1 to polysomes.