| Autor: |
Goswami P; Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, United States., Banks CAS; Stowers Institute for Medical Research, Kansas City, Missouri 64110, United States., Thornton J; Stowers Institute for Medical Research, Kansas City, Missouri 64110, United States., Bengs BD; Department of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, Kansas 66103, United States., Sardiu ME; Department of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, Kansas 66103, United States., Florens L; Stowers Institute for Medical Research, Kansas City, Missouri 64110, United States., Washburn MP; Stowers Institute for Medical Research, Kansas City, Missouri 64110, United States. |
| Abstrakt: |
Sin3 is an evolutionarily conserved repressor protein complex mainly associated with histone deacetylase (HDAC) activity. Many proteins are part of Sin3/HDAC complexes, and the function of most of these members remains poorly understood. SAP25, a previously identified Sin3A associated protein of 25 kDa, has been proposed to participate in regulating gene expression programs involved in the immune response but the exact mechanism of this regulation is unclear. SAP25 is not expressed in HEK293 cells, which hence serve as a natural knockout system to decipher the molecular functions uniquely carried out by this Sin3/HDAC subunit. Using molecular, proteomic, protein engineering, and interaction network approaches, we show that SAP25 interacts with distinct enzymatic and regulatory protein complexes in addition to Sin3/HDAC. Additional proteins uniquely recovered from the Halo-SAP25 pull-downs included the SCF E3 ubiquitin ligase complex SKP1/FBXO3/CUL1 and the ubiquitin carboxyl-terminal hydrolase 11 (USP11). Furthermore, mutational analysis demonstrates that distinct regions of SAP25 participate in its interaction with USP11, OGT/TETs, and SCF(FBXO3). These results suggest that SAP25 may function as an adaptor protein to coordinate the assembly of different enzymatic complexes to control Sin3/HDAC-mediated gene expression. The data were deposited with the MASSIVE repository with the identifiers MSV000093576 and MSV000093553. |
