The tumor suppressor gene RB regulates cell proliferation at the G1/S transition of the cell cycle. The retinoblastoma protein pRB associates with both HDAC-dependent and independent mechanisms to actively repress E2F-dependent genes required for entry into S phase. The retinoblastoma binding protein 1 RBP1 recruits the mSin3A/HDAC1 co-repressor complex to the pocket of pRB at growth arrest and accounts for the majority of the HDAC activity associated with pRB. However, transcriptional repression by RBP1 also involves HDAC-independent activities because repression is only partially relieved by the HDAC inhibitor Trichostatin A. This activity is mediated in part by residues 241 to 452 of RBP1 designated as the R1 domain. Hypermapping studies on the previously defined R1 domain of RBP1 revealed that amino acids 400 to 452 of RB1 are sufficient to mediate HDAC-independent repression. Inspection of the minimal R1 region located two copies of the SUMO consensus motif Psi-K-X-E and subsequent experiments demonstrated that the R1 domain is post-translationally modified by SUMO on lysine 418 and 444. In addition, transcriptional repression by the R1 domain was abrogated by either mutagenesis of both SUMO acceptor lysines or in the presence of a SUMO specific protease implying that SUMO modification modulates HDAC-independent transcriptional repression by RBP1.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.80869 |
| Date | January 2003 |
| Creators | Roy, Jean-Sébastien |
| Contributors | Branton, Philip E. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002031514, proquestno: AAIMQ98734, Theses scanned by UMI/ProQuest. |
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