HCCRBP-1 directly interacting with HCCR-1 induces tumorigenesis through P53 stabilization

✍ Scribed by Seon-Ah Ha; Seung Min Shin; Yong Jin Lee; Sanghee Kim; Hyun Kee Kim; Hong Namkoong; Heejeong Lee; Youn Soo Lee; Young-Seok Cho; Yong Gyu Park; Hae Myung Jeon; Changkyu Oh; Jin Woo Kim

• Book ID: 102863575
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 748 KB
• Volume: 122
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23146

✦ Synopsis

Abstract

Oncogene HCCR‐1 functions as a negative regulator of the p53 and contributes to tumorigenesis of various human tissues. HCCR transgenic mice developed breast cancers but it is unknown how HCCR‐1 contributes to human tumorigenesis. This study identified a HCCR‐1‐binding protein 1 (HCCRBP‐1) as an HCCR binding partner by performing yeast two hybrid screening. Their endogenous interaction was further confirmed by coimmunoprecipitation experiments. These two proteins colocalized in the mitochondria. HCCRBP‐1 was overexpressed in various human tumors. In addition, HCCRBP‐1 alone converted NIH/3T3 cells into tumor cells in combination with no other oncogenes. HCCRBP‐1 induced tumorigenesis by markedly activating PKC activities but decreasing the pro‐apoptotic PKCα and PKCδ isoform levels. We observed that p53 stabilization also occurred with functional impairment in HCCRBP‐1‐transfected 293 cells, as indicated by defective induction of p21, MDM2 and bax. Indeed, HCCRBP‐1 decreased p21 promoter activity probably via p53 stabilization leading to the defective function. These results indicate that HCCRBP‐1 oncogene induces p53 stabilization and thereby contributes to tumorigenesis. © 2007 Wiley‐Liss, Inc.