): The long-term goal of the applicant is to understand how cells decide to undergo cell-cycle withdrawal and terminal differentiation, especially during myogenesis, where these processes are irreversible. The adenovirus E1A oncoprotein targets certain regulators of cell proliferation and differentiation. Among these are the E1A-associated proteins, p300 and CREB-binding protein (CBP). p300 and CBP form part of a family of transcriptional co-activators and mediate signal responsive transcription and probably act at a nodal point in the coordination of exit from the cell cycle and terminal differentiation. Proteins that bind to p300/CBP are likely to be involved in this form of regulation. A 31 kd protein (p31) that binds in vivo to an evolutionarily conserved domain in p300 and CBP has been identified. The interaction is detected in proliferating myoblasts, but not in differentiated myocytes. Therefore, p31 seems likely to play a significant role in p300/CBP function.
The aim of this study is to search for the functional significance of p31-p300/CBP complex formation and to learn whether complex formation is linked to the regulation of cell cycle withdrawal and terminal differentiation.
The specific aims of this study are to: 1) Clone and sequence the cDNA encoding a 31 kd protein that interacts in vivo with p300 and CBP; 2) Determine whether p31 is a transcription factor or a known protein which operates in a different manner; and 3) Search for a role for p31-p300/CBP complexes in the control of cell growth and terminal differentiation.
