The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity.
Sam68 (Src-associated in mitosis; 68 kDa) is a member of the STAR (signal transduction and activation of RNA) family of KH domain-containing RNA binding proteins. Accumulating evidence suggests that it plays an important role in cell cycle control. Tyrosine phosphorylation by Src family kinases and breast tumor kinase can negatively regulate its RNA binding activity. To date, there are no reports of a factor, such as a phosphatase, which can positively regulate Sam68 association with RNA. Acetylation is a reversible post-translational modification known to influence the activity of DNA binding proteins. However, acetylation of a cellular RNA binding protein as a mechanism for regulating its activity has not yet been reported. Here we demonstrate Sam68 to be acetylated in vivo. A screen of several human mammary epithelial cell lines revealed variations in Sam68 acetylation. Interestingly, the highest level of acetylation was found in tumorigenic breast cancer cell lines. The screen also showed a positive correlation between Sam68 acetylation and its ability to bind RNA. The acetyltransferase CBP was shown to acetylate Sam68 and enhance its binding to poly(U) RNA. These results suggest that Sam68 association with RNA substrates may be positively regulated by acetylation, and that enhanced acetylation and RNA binding activity of Sam68 may play a role in tumor cell proliferation.
Babic
Ivan
I
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary AB, Canada T2N 4N1. ibabic@ucalgary.ca
Jakymiw
Andrew
A
Fujita
Donald J
DJ
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D050882:CREB-Binding Protein; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; C489559:KHDRBS1 protein, human; C513253:Khdrbs1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D012313:RNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494364:Crebbp protein, mouse; D006655:Histone Deacetylases