The goal of this proposal is to characterize the transcriptional regulatory circuits and control the development and maintenance of the vertebrate skeletal muscle phenotype. Characterization of the novel bHLG factor (Mist1) and the muscle-specific LIM protein (MLP) as well as identifying the target genes of the MRFs during the establishment of the myogenic lineage is critical to dissecting the regulatory networks that control skeletal myogenesis. The PI proposes to: 1) examine how Mist1 inhibits MRF activity; 2) establish the mechanism(s) by which the muscle LIM protein, MSP, enhances MRF activity and 3) identify true myoblast-specific genes that are regulated by the MRFs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR041115-09
Application #
6374933
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Lymn, Richard W
Project Start
1993-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2003-07-31
Support Year
9
Fiscal Year
2001
Total Cost
$292,403
Indirect Cost
Name
Purdue University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Mitin, Natalia Y; Ramocki, Melissa B; Zullo, Alfred J et al. (2004) Identification and characterization of rain, a novel Ras-interacting protein with a unique subcellular localization. J Biol Chem 279:22353-61
Rukstalis, J Michael; Kowalik, Agnes; Zhu, Liqin et al. (2003) Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1. J Cell Sci 116:3315-25
Pin, Christopher L; Konieczny, Stephen F (2002) A fast fiber enhancer exists in the muscle regulatory factor 4 gene promoter. Biochem Biophys Res Commun 299:7-13
Wyzykowski, Jeffrey C; Winata, Therry I; Mitin, Natalia et al. (2002) Identification of novel MyoD gene targets in proliferating myogenic stem cells. Mol Cell Biol 22:6199-208
Mitin, N; Kudla, A J; Konieczny, S F et al. (2001) Differential effects of Ras signaling through NFkappaB on skeletal myogenesis. Oncogene 20:1276-86
Pin, C L; Rukstalis, J M; Johnson, C et al. (2001) The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity. J Cell Biol 155:519-30
Pin, C L; Bonvissuto, A C; Konieczny, S F (2000) Mist1 expression is a common link among serous exocrine cells exhibiting regulated exocytosis. Anat Rec 259:157-67
Pena, T L; Chen, S H; Konieczny, S F et al. (2000) Ras/MEK/ERK Up-regulation of the fibroblast KCa channel FIK is a common mechanism for basic fibroblast growth factor and transforming growth factor-beta suppression of myogenesis. J Biol Chem 275:13677-82
Pin, C L; Lemercier, C; Konieczny, S F (1999) Cloning of the murine Mist1 gene and assignment to mouse chromosome band 5G2-5G3. Cytogenet Cell Genet 86:219-22
Ramocki, M B; White, M A; Konieczny, S F et al. (1998) A role for RalGDS and a novel Ras effector in the Ras-mediated inhibition of skeletal myogenesis. J Biol Chem 273:17696-701

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