Regulation of Sam68 activity by small heat shock protein 22.
Sam68 associates with c-Src kinase during mitosis. We previously demonstrated that Sam68 functionally replaces and/or synergizes with HIV-1 Rev in rev response element (RRE)-mediated gene expression and virus production. Furthermore, we reported that knockdown of Sam68 inhibited Rev-mediated RNA export and it is absolutely required for HIV-1 production. In the present study, we identified small heat shock protein, hsp22, as a novel interacting partner of Sam68. Hsp22 binds to Sam68 in vitro and in vivo. Overexpression of hsp22 significantly inhibits Sam68-mediated RRE- as well as CTE (constitutive transport element)-dependent reporter gene expression. Furthermore, exposing 293T cells to heat shock inhibits Sam68/RRE function by virtue of elevating hsp22. The critical domain of hsp22 that interacts with Sam68 resides between amino acids 62 and 133. Our studies provide evidence for the first time that hsp22 specifically binds to Sam68 and modulates its activity, thus playing a role in the post-transcriptional regulation of gene expression.
Badri
Kameswara R
KR
Department of Immunology and Microbiology, Wayne State University-School of Medicine, Detroit, Michigan 48201, USA.
Modem
Suhasini
S
Gerard
Herve C
HC
Khan
Insia
I
Bagchi
Mihir
M
Hudson
Alan P
AP
Reddy
Thipparthi R
TR
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; C489559:KHDRBS1 protein, human; D018832:Molecular Chaperones; D016601:RNA-Binding Proteins; D017346:Protein Serine-Threonine Kinases