Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization

Title
Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization
Author(s)
김지회김충권[김충권]이상배[이상배]Trunong L. X. Nguyen[Trunong L. X. Nguyen]이경훈[이경훈]음성희[음성희]안지인[안지인]
Keywords
P53 UBIQUITINATION; TUMOR-SUPPRESSOR; MDM2; EBP1; PHOSPHORYLATION; DEGRADATION; ONCOPROTEIN; INHIBITION; PROMOTES; PATHWAY
Issue Date
201201
Publisher
ELSEVIER INC
Citation
EXPERIMENTAL CELL RESEARCH, v.318, no.2, pp.136 - 143
Abstract
p48 is a long isoform of the ErbB3 binding protein that has oncogenic functions including promotion of carcinogenesis and induction of malignant transformation through negative regulation of tumor suppressor p53. Here, we show that high level of p48 protein expression leads to enhance HDM2 phosphorylation by Akt and inhibits the self-ubiquitination of HDM2 by up-regulation of Akt activity, thereby promoting its protein stability. Moreover, p48 expression leads to accumulated nuclear localization of HDM2, whereas p48 depletion disturbs its nuclear localization. Hence, higher expression of p48 in cancer cells reduces p53 levels through modulation of HDM2 nuclear localization and protein stability via regulation of its Akt-mediated phosphorylation. (C) 2011 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/29995http://dx.doi.org/10.1016/j.yexcr.2011.08.013
ISSN
0014-4827
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생명공학부 > 생명공학부 > Articles
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