Transcriptional repression of cyclin‐dependent kinase inhibitor p21 gene by phospholipase D1 and D2

FEBS Letters

Kwun, Hyun Jin²  Min, Do Sik¹  Jang, Kyung Lib²  Lee, Jae Hwa² 

[1] Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea;Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, South Korea

关键词: Carcinogenesis;    Cyclin-dependent kinase inhibitor;    Cell cycle;    p21;    p53;    Phospholipase D;    Sp1;    CDK;    cyclin-dependent kinase;    PIP2;    phosphatidylinositol 4;    5-bisphosphate;    PLD;    phospholipase D;    PKC;    protein kinase C;   

DOI  :  10.1016/S0014-5793(03)00446-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phospholipase D (PLD) is known to stimulate cell cycle progression and to transform murine fibroblast cells into tumorigenic forms, although the precise mechanisms are not elucidated. In this report, we demonstrated that both PLD1 and PLD2 repressed expression of cyclin-dependent kinase inhibitor p21 gene in an additive manner. The phospholipase activity of PLDs was important for the effect. PLD1 repressed the p21 promoter by decreasing the level of p53, whereas PLD2 via a p53-independent pathway through modulating Sp1 activity. Taken together, we suggest that PLD isozymes stimulate cell growth by repressing expression of p21 gene, which may ultimately lead to carcinogenesis.

【 授权许可】

Unknown