Transcriptional repression of cyclin-dependent kinase inhibitor p21 gene by phospholipase D1 and D2.
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.
Kwun
Hyun Jin
HJ
Department of Microbiology, College of Natural Sciences, Pusan National University, South Korea.
Lee
Jae Hwa
JH
Min
Do Sik
DS
Jang
Kyung Lib
KL
D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D010739:Phospholipase D / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D020033:Protein Isoforms; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1