Role of Promyelocytic Leukaemia Zinc Finger (PLZF) in cell proliferation and Cyclin Dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) gene repression [Cell Biology]

May 12th, 2014 by Choi, W.-I., Kim, M.-Y., Jeon, B.-N., Koh, D.-I., Yun, C.-O., Li, Y., Lee, C.-E., Oh, J., Kim, K., Hur, M.-W.

PLZF is a transcription repressor which was initially isolated as a fusion protein with RARĪ±. PLZF is aberrantly overexpressed in various human solid tumors, such as clear cell renal carcinoma, glioblastoma, and seminoma. PLZF causes cellular transformation of NIH3T3 cells and increases cell proliferation in several cell types. PLZF also increases tumor growth in mouse xenograft tumor model. PLZF may stimulate cell proliferation by controlling expression of the genes of the p53 pathway (ARF, TP53, and CDKN1A). We found that PLZF can directly repress transcription of CDKN1A encoding p21, a negative regulator of cell cycle progression. PLZF binds to the proximal Sp1-binding GC-box 5/6 and the distal p53-responsive elements of CDKN1A promoter to repress transcription. Interestingly, PLZF interacts with Sp1 or p53 and competes with Sp1 or p53. PLZF interacts with corepressors, such as mSin3A, NCoR and SMRT, thereby deacetylates Ac-H3 and Ac-H4 histones at the CDKN1A promoter, which indicated the involvement of corepressor-HDACs complex in transcription repression by PLZF. Also, PLZF represses transcription of TP53 and also decreases p53 protein stability by ubiquitination. PLZF may act as a potential a proto-oncoprotein in various cell types.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Role of Promyelocytic Leukaemia Zinc Finger (PLZF) in cell proliferation and Cyclin Dependent Kinase Inhibitor 1A (p21WAF/CDKN1A) gene repression [Cell Biology]