期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 21, 期 15, 页码 5041-5049出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.21.15.5041-5049.2001
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资金
- NIDDK NIH HHS [R01 DK052913, DK52913, R01 DK052913-06, R56 DK052913] Funding Source: Medline
Sp1-like proteins are defined by three highly homologous C2H2 zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta -inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (alpha -HRM) located within the repression domain (R1) of TIEG2. This alpha -HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 alpha -HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the alpha -HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The alpha -HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the alpha -HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the alpha -HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.
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