Abstract

The aims of this proposal are to define how human MAD2 (hsMAD2) functions as a mitotic checkpoint gene and to determine if disruption of hsMAD2 contributes to the generation of neoplasia in mouse models. hsMAD2 is the human homolog of a mitotic checkpoint gene first identified in budding yeast (scMAD2). The investigator proposes to test the hypothesis is that the biochemical mechanism underlying human MAD2 checkpoint function is its ability to inhibit the APC through its interactions with Cdc16 and Cdc27. In addition, MAD2 will be disrupted in both ES cells and mice to determine the contribution made by MAD2 to mitotic checkpoint control in mammalian cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054601-03
Application #
2910259
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1997-05-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2001-04-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Horwitz, Briana N; Marceau, Kristine; Narusyte, Jurgita et al. (2015) Parental criticism is an environmental influence on adolescent somatic symptoms. J Fam Psychol 29:283-9
Michel, Loren; Diaz-Rodriguez, Elena; Narayan, Gopeshwar et al. (2004) Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells. Proc Natl Acad Sci U S A 101:4459-64
Wassmann, Katja; Liberal, Vasco; Benezra, Robert (2003) Mad2 phosphorylation regulates its association with Mad1 and the APC/C. EMBO J 22:797-806
Hernando, E; Orlow, I; Liberal, V et al. (2001) Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. Int J Cancer 95:223-7
Wassmann, K; Benezra, R (2001) Mitotic checkpoints: from yeast to cancer. Curr Opin Genet Dev 11:83-90
Dobles, M; Liberal, V; Scott, M L et al. (2000) Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2. Cell 101:635-45
Wassmann, K; Benezra, R (1998) Mad2 transiently associates with an APC/p55Cdc complex during mitosis. Proc Natl Acad Sci U S A 95:11193-8