title: 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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Wen-Horng
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, USA Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Childress
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA geahlen@purdue.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Geahlen
mesh_terms: D002470:Cell Survival; D004249:DNA Damage; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D061986:MCF-7 Cells; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000072377:Syk Kinase; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism; D000097796:Nucleolin
chemical_list: D006861:Hydrogen Peroxide; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000072377:Syk Kinase; D051020:bcl-X Protein; D000097796:Nucleolin; C494811:BCL2L1 protein, human; C000606896:SYK protein, human
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