title: Long isoform of ErbB3 binding protein, p48, mediates protein kinase B/Akt-dependent HDM2 stabilization and nuclear localization.
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.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 440-746, Republic of Korea.
authors.forename: Chung Kwon
authors.initials: CK
authors.lastname: Kim
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Lee
authors.forename: Truong L X
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Um
authors.forename: Jihoe
authors.initials: J
authors.lastname: Kim
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C101633:PA2G4 protein, human; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt