Differential binding of Sin3 interacting repressor domains to the PAH2 domain of Sin3A.
The Sin3 interacting domain (SID), originally described in the Mad family of repressors, is a novel transcriptional repressor domain that binds the PAH2 domain of corepressors Sin3A and Sin3B with high affinities. The conserved SID-like domains are reportedly present in five KLF proteins. However, the KLF SIDs and the Mad SIDs can be classified into two subtypes according to sequence similarity. Here, we report the finding from computational and experimental studies that the two subtypes of SID domains bind differentially to Sin3A. This finding offers insights into a mechanism of cell growth regulation by interactions of different subtypes of SID-containing repressor proteins with Sin3. It also provides the structural basis for developing selective modulators of Sin3.
Pang
Yuan-Ping
YP
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Foundation for Medical Education and Research, 200 First Street SW, Rochester, MN 55905, USA. pang@mayo.edu
Kumar
Ganesh A
GA
Zhang
Jin-San
JS
Urrutia
Raul
R
D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D018797:Cell Cycle Proteins; D003198:Computer Simulation; D017124:Conserved Sequence; D006655:Histone Deacetylases; D051741:Kruppel-Like Transcription Factors; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C115117:KLF11 protein, human; C486423:KLF13 protein, human; D051741:Kruppel-Like Transcription Factors; C501382:MAD1 protein, S cerevisiae; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; C099683:SIN3A transcription factor; C492042:SIN3B protein, human; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex