| First Author | Basu S | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 5 | Pages | 1433-8 |
| PubMed ID | 19164764 | Mgi Jnum | J:144477 |
| Mgi Id | MGI:3831020 | Doi | 10.1073/pnas.0804863106 |
| Citation | Basu S, et al. (2009) Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A 106(5):1433-8 |
| abstractText | Gfi-1 is a nuclear zinc finger (ZF) transcriptional repressor that plays an important role in hematopoiesis and inner ear development, and has been implicated in lymphomagenesis. Gfi-1 represses transcription by directly binding to the consensus DNA sequence in the promoters of its target genes. We report here an alternative mechanism by which Gfi-1 represses CDKN2B encoding p15(INK4B). Gfi-1 does not directly bind to CDKN2B, but interacts with Miz-1 and, via Miz-1, is recruited to the core promoter of CDKN2B. Miz-1 is a POZ-ZF transcription factor that has been shown to mediate transcriptional repression by c-Myc. Like c-Myc, upon recruitment to the CDKN2B promoter, Gfi-1 represses transcriptional activation of CDKN2B by Miz-1 and in response to TGFbeta. Consistent with its role in repressing CDKN2B transcription, knockdown of Gfi-1 in human leukemic cells or deficiency of Gfi-1 in mouse bone marrow cells results in augmented expression of p15(INK4B). Notably, Gfi-1 and c-Myc are both recruited to the CDKN2B core promoter and act in collaboration to repress CDKN2B. Our data reveal a mechanism of transcriptional repression by Gfi-1 and may have important implications for understanding the roles of Gfi-1 in normal development and tumorigenesis. |
