HCCRBP-1 directly interacting with HCCR-1 induces tumorigenesis through P53 stabilization |
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Authors: | Ha Seon-Ah Shin Seung Min Lee Yong Jin Kim Sanghee Kim Hyun Kee Namkoong Hong Lee Heejeong Lee Youn Soo Cho Young-Seok Park Yong Gyu Jeon Hae Myung Oh Changkyu Kim Jin Woo |
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Affiliation: | Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea. |
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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 PKC alpha and PKC delta 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. |
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Keywords: | oncogene HCCR‐1 HCCRBP‐1 tumorigenesis p53 |
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