Our long term goal is to decipher the molecular mechanisms that mediate cell growth, proliferation and differentiation. The central theme of this program project is firmly rooted in the conviction that transcriptional regulation provides the key link in triggering the complex cellular processes require to initiate cell growth. Project 5 """"""""Control of cellular proliferation by cAMP"""""""": This program proposes to dissect the molecular mechanism by which cAMP can act both as an inhibitor and mitogen for cell proliferation. Project 6 """"""""Activation of TCR alpha-chain enhancer by the LEF-1 HMG protein"""""""":
The aim of this project is to define the molecular mechanisms involved in the transcription of alpha chain of T cell receptor (TCR alpha) gene. Project 3 """"""""Transcriptional regulation of T cell receptor alpha gene"""""""": Experiments are proposed to study how TCR alpha gene is transcriptionally regulated during T-lymphocyte development, with particular focus on the role of enhancer sequences which lie at a distance of 69 kb. Project 7 """"""""Proto-oncogene signalling pathways and steroid hormone receptors"""""""": This proposal is to understand the molecular mechanisms by which glucocorticoids and retinoids repress transcription by early response genes like Fos, Jun and NF-kappaB/Rel. Project 8 """"""""Structural analysis of cell growth regulators"""""""": The three-dimensional structure of receptor phospho tyrosine phosphatase alpha (RPTPalpha) and IkappaBalpha or p65/IkappaBalpha will be determined. In addition to the seven projects, there are three core facilities. Core 9001 """"""""Peptide synthesis and antibody production"""""""": This core will be involved in synthesis of peptides and generation of antibodies. Core 9002 """"""""Characterization of proteins and their post-translational modifications"""""""": This core will be responsible for determining primary amino acid sequences.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA054418-09
Application #
2894881
Study Section
Cancer Centers and Research Programs Review Committee (CCRP)
Program Officer
Mietz, Judy
Project Start
1991-06-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Carrano, Andrea C; Dillin, Andrew; Hunter, Tony (2014) A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans. Nat Commun 5:3772
Altarejos, Judith Y; Montminy, Marc (2011) CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol 12:141-51
Carrano, Andrea C; Liu, Zheng; Dillin, Andrew et al. (2009) A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature 460:396-9
Bres, Vanessa; Yoh, Sunnie M; Jones, Katherine A (2008) The multi-tasking P-TEFb complex. Curr Opin Cell Biol 20:334-40
Fryer, Christy J; White, J Brandon; Jones, Katherine A (2004) Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16:509-20
Tutter, A; McAlpine, G S; Jones, K A (1999) Mechanism of chromatin recognition and transcriptional regulation by LEF-1 and the Wnt/Wg-responsive LEF-1:beta-catenin complex. Cold Spring Harb Symp Quant Biol 64:445-52
Bagga, R; Armstrong, J A; Emerson, B M (1998) Role of chromatin structure and distal enhancers in tissue-specific transcriptional regulation in vitro. Cold Spring Harb Symp Quant Biol 63:569-76
Bagga, R; Emerson, B M (1997) An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro. Genes Dev 11:629-39
Carlsson, P; Waterman, M L; Jones, K A (1993) The hLEF/TCF-1 alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCR alpha enhancer in T cells. Genes Dev 7:2418-30