Accession Number : ADA443685


Title :   Smad Acetylation: A New Level of Regulation in TGF-Beta Signaling


Descriptive Note : Annual summary 7 Jan 2004-30 Jun 2005


Corporate Author : CALIFORNIA UNIV BERKELEY


Personal Author(s) : Tu, Andrea W


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a443685.pdf


Report Date : Jul 2005


Pagination or Media Count : 11


Abstract : The transforming growth factor BETA (TGF-BETA) signaling pathway is an essential pathway that results in cell growth arrest when initiated in most epithelial cells. Initiation of TGF-BETA receptors leads to the phosphorylation and translocation of the Smad proteins, the major TGF-BETA intracellular signaling molecule, to the nucleus where transcription of TGF-BETA target genes occur. Aberrations in the Smad proteins are present in many breast cancers indicating their importance. Understanding how post-translational modification such as phosphorylation and acetylation regulate pathways will increase our knowledge of how a normal cell becomes cancerous and may provide insight into novel therapeutics. This proposal suggests a series of experiments designed to study whether acetylation of Smad proteins occurs. Our lab has determined that Smad2, but not Smad3, can be acetylated by the acetyltransferase protein p300 in vivo and in vitro. The residues required for acetylation have been mapped and mutated resulting in a Smad2 mutant that cannot be acetylated. This mutant still retains its ability to become phosphorylated and bind Smad4 without affecting its stability. However, preliminary studies suggest a larger cytoplasmic fraction of the mutant Smad2 upon TGF-BETA treatment in comparison to the wild type Smad2 protein.


Descriptors :   *BREAST CANCER , EPITHELIUM , PROTEINS , ARRESTING(PROCESS) , IN VITRO ANALYSIS , THERAPY , CELLS(BIOLOGY) , NUCLEI , GROWTH(PHYSIOLOGY) , PHOSPHORYLATION , TRANSLOCATION , ACETYLATION


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE