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- Title
A role of Miz-1 in Gfi-1-mediated transcriptional repression of CDKN1A.
- Authors
Liu, Q.; Basu, S.; Qiu, Y.; Tang, F.; Dong, F.
- Abstract
Zinc-finger (ZF) transcriptional repressor growth factor independence 1 (Gfi-1) has an important role in hematopoiesis and inner ear development, and also functions as an oncoprotein that cooperates with c-Myc in lymphomagenesis. Gfi-1 represses transcription by directly binding to conserved sequences in the promoters of its target genes. CDKN1A encoding p21Cip1 has been identified as a Gfi-1 target gene and has been shown to contain Gfi-1 binding sites in the upstream promoter region. We show here that Gfi-1 represses CDKN1A in a manner that is independent of its DNA binding activity. Gfi-1 interacts with POZ-ZF transcription factor Miz-1, originally shown to be a c-Myc-interacting partner, and through Miz-1 binds to the CDKN1A core promoter. Interestingly, Gfi-1 and c-Myc, through Miz-1, form a ternary complex on the CDKN1A promoter, and function in collaboration to repress CDKN1A. Gfi-1 knockdown results in enhanced levels of p21Cip1 and attenuated cell proliferation. Notably, similar to c-Myc, the expression of Gfi-1 is downregulated by transforming growth factor-β (TGFβ) and the level of Gfi-1 influences the response of cells to the cytostatic effect of TGFβ. Our data reveal an important mechanism by which Gfi-1 regulates cell proliferation and may also have implications for understanding the role of Gfi-1 in lymphomagenesis.
- Subjects
GENETIC repressors; TRANSFORMING growth factors; HEMATOPOIESIS; TRANSCRIPTION factors; ZINC-finger proteins; CELL proliferation; GENES
- Publication
Oncogene, 2010, Vol 29, Issue 19, p2843
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.48