The 90-kDa heat shock protein stabilizes the polysomal ribonuclease 1 mRNA endonuclease to degradation by the 26S proteasome.
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.
Peng
Yong
Y
Department of Molecular and Cellular Biochemistry, RNA Group and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Liu
Xiaoqiang
X
Schoenberg
Daniel R
DR
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001665:Binding Sites; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004720:Endonucleases / Q000737:chemistry / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008954:Models, Biological; D011132:Polyribosomes / Q000187:drug effects / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017434:Protein Structure, Tertiary; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D012333:RNA, Messenger; D004720:Endonucleases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C001277:geldanamycin