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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.

SUBMITTER: Wang WH

PROVIDER: S-EPMC4187708 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Syk interacts with and phosphorylates nucleolin to stabilize Bcl-x(L) mRNA and promote cell survival.

Wang Wen-Horng WH Childress Michael O MO Geahlen Robert L RL

Molecular and cellular biology 20140804 20

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 n ...[more]

PMID: 25092868

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