Syk Interacts with and Phosphorylates Nucleolin To Stabilize Bcl-x_L mRNA and Promote Cell Survival

Abstract

The Syk protein tyrosine kinase, a well-characterized regulator of immune cell function, plays an increasingly recognized role in tumorigenesis as a promoter of cell survival in both hematological and nonhematological malignancies. We show here that the expression of Syk in MCF7 or MDA-MB-231 breast cancer cells or in DG75 B-lymphoma cells protects cells from apoptosis induced by oxidative or genotoxic stress by stabilizing the mRNA for Bcl-x_L, an antiapoptotic protein. Syk binds robustly to nucleolin and phosphorylates it on tyrosine, enhancing its ability to bind the Bcl-x_L mRNA. Consequently, reducing the level of nucleolin by RNA interference attenuates the ability of Syk to protect cells from stress-induced cell death.

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SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00937-14.

ACKNOWLEDGMENTS

This work was supported by Public Health Services grant AI098132 from the National Institute of Allergy and Infectious Diseases. The DNA sequencing facility was supported by NCI CCSG CA23168 to the Purdue University Center for Cancer Research.