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The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity

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Abstract

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.

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Acknowledgements

We thank T Kouzarides for providing the GST-CBP (HAT domain) plasmid and R Goodman for the mouse CBP-HA cDNA. We also thank J Bjorge for critical reading of the manuscript and technical advice. This work was supported by grants to DJF from the National Cancer Institute of Canada (NCIC), the Canadian Breast Cancer Research Alliance, the Canadian Institutes of Health Research (CIHR), and the Canadian Breast Cancer Foundation (AB/NWT Chapter). IB was supported by a CIHR Doctoral Research Award and an Alberta Heritage Foundation for Medical Research (AHFMR) Studentship Award; AJ was supported by studentship awards from CIHR and AHFMR; DJF is a Scientist of the AHFMR.

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  1. Andrew Jakymiw

    Present address: Department of Oral Biology, University of Florida, Gainesville, FL, 32610, USA

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  1. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, T2N 4N1, AB, Canada

    Ivan Babic, Andrew Jakymiw & Donald J Fujita

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  1. Ivan Babic
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Correspondence to Ivan Babic or Donald J Fujita.

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Babic, I., Jakymiw, A. & Fujita, D. The RNA binding protein Sam68 is acetylated in tumor cell lines, and its acetylation correlates with enhanced RNA binding activity. Oncogene 23, 3781–3789 (2004). https://doi.org/10.1038/sj.onc.1207484

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