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Phosphorylation of the N‐terminal domain of p48 Ebp1 by CDK2 is required for tumorigenic function of p48
Author(s) -
Ko Hyo Rim,
Kim Chung Kwon,
Ahn JeeYin
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22203
Subject(s) - biology , phosphorylation , gene isoform , microbiology and biotechnology , cell growth , cyclin dependent kinase 2 , mutant , carcinogenesis , kinase , serine , biochemistry , protein kinase a , gene
The long isoform of ErbB3 binding protein 1 (Ebp1), p48, strongly promotes tumorigenesis of glioblastoma, accelerating cell proliferation and transformation, while the short isoform, p42, which lacks the N‐terminal 54 amino acids, inhibits tumor growth. However, it is unclear if the N‐terminal domain of p48 regulates the oncogenic function of p48. Here, we show that p48, but not p42, interacts with cyclin‐dependent kinase 2 (CDK2) through its N‐terminal domain, resulting in the specific phosphorylation of serine 34 of p48. Overexpression of wild‐type p48 greatly enhanced tumor cell growth, whereas phospho‐ablated mutant S34A of p48, which is mutated at the CDK2 phosphorylation site, antagonizes cell proliferation and transformation. Moreover, phospho‐ablated mutant S34A abrogated the ability of p48 to accelerate tumor cell growth in a mouse engraft model. Thus, our findings indicate that p48Ebp1 acts as an oncoprotein through selective interaction and/or modification of the N‐terminal domain that does not exist in its short isoform p42. © 2014 Wiley Periodicals, Inc.