Abstract

c-, N- and L-Myc belong to a superfamily of related bHLH/LZ proteins and function in part as sequence-specific transcription factors involved in the regulation of genes controlling processes of cellular growth, differentiation and programmed cell death. Activities of Myc are highly dependent upon its dimerization with Max and are opposed by two other bHLH/LZ proteins, Mad and Mxi1. The contrasting biochemical properties of Myc and Mad or Mxi1 have led to a working model for the regulation of Myc- responsive genes in which transactivation-inert Mad or Mxi1 proteins compete with Myc for binding to both Max and to common target sequences. The goal of this proposal is to develop several biological systems for the elucidation of the functional interrelationships among members of the Myc superfamily and of how these interactions impact on the regulation of downstream effector genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD028317-07
Application #
2889047
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Hewitt, Tyl
Project Start
1991-09-01
Project End
2000-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

de Alboran, I M; O'Hagan, R C; Gartner, F et al. (2001) Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14:45-55
Hemann, M T; Rudolph, K L; Strong, M A et al. (2001) Telomere dysfunction triggers developmentally regulated germ cell apoptosis. Mol Biol Cell 12:2023-30
Lee, K H; Rudolph, K L; Ju, Y J et al. (2001) Telomere dysfunction alters the chemotherapeutic profile of transformed cells. Proc Natl Acad Sci U S A 98:3381-6
O'Hagan, R C; Ohh, M; David, G et al. (2000) Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression. Genes Dev 14:2185-91
Artandi, S E; DePinho, R A (2000) A critical role for telomeres in suppressing and facilitating carcinogenesis. Curr Opin Genet Dev 10:39-46
O'Hagan, R C; Schreiber-Agus, N; Chen, K et al. (2000) Gene-target recognition among members of the myc superfamily and implications for oncogenesis. Nat Genet 24:113-9
Bardeesy, N; Wong, K K; DePinho, R A et al. (2000) Animal models of melanoma: recent advances and future prospects. Adv Cancer Res 79:123-56
Wong, K K; Chang, S; Weiler, S R et al. (2000) Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet 26:85-8
Malynn, B A; de Alboran, I M; O'Hagan, R C et al. (2000) N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes Dev 14:1390-9
Rudolph, K L; Chang, S; Millard, M et al. (2000) Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. Science 287:1253-8

Showing the most recent 10 out of 27 publications