HCCRBP-1 directly interacting with HCCR-1 induces tumorigenesis through P53 stabilization.
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.
Ha
Seon-Ah
SA
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul 137-040, Korea.
Shin
Seung Min
SM
Lee
Yong Jin
YJ
Kim
Sanghee
S
Kim
Hyun Kee
HK
Namkoong
Hong
H
Lee
Heejeong
H
Lee
Youn Soo
YS
Cho
Young-Seok
YS
Park
Yong Gyu
YG
Jeon
Hae Myung
HM
Oh
Changkyu
C
Kim
Jin Woo
JW
D000818:Animals; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D013347:Subcellular Fractions; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism
C516325:HCCR1 protein, mouse; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase