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Transcriptional repression of cyclin‐dependent kinase inhibitor p21 gene by phospholipase D1 and D2
Author(s) -
Kwun Hyun Jin,
Lee Jae Hwa,
Min Do Sik,
Jang Kyung Lib
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00446-0
Subject(s) - pld2 , phospholipase d , psychological repression , cyclin d1 , cyclin dependent kinase 4 , cancer research , carcinogenesis , chemistry , kinase , microbiology and biotechnology , cyclin dependent kinase 3 , biology , isozyme , cyclin d , cell cycle , cyclin dependent kinase 2 , signal transduction , gene , gene expression , biochemistry , protein kinase a , enzyme , phosphatidic acid , phospholipid , membrane
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.