The regulation of mammalian cell growth is governed by both positive and negative signaling pathways. The retinoblastoma (Rb) gene encodes a family of nuclear phosphoproteins, termed p105-Rb, whose function is thought to be to limit or constrain cell proliferation. The mechanism by which Rb-mediated growth restraint is imposed is currently unknown. Furthermore, the proteins and biochemical signals that regulate pl05-Rb activity have yet to be characterized. Given the importance of Rb inactivation in the etiology of various human tumors and the widespread distribution of plO5-Rb in all mammalian cells , it is clear that plO5-Rb plays a central role in regulating normal cell growth. To determine the function of plO5-Rb and to define its contribution towards negative-growth regulation we propose to address the following specific aims: 1. Through biochemical and genetic means we will identify and clone genes encoding proteins that interact with plO5-Rb. These proteins will be characterized for their biochemical properties, distribution, and role in regulating or mediating Rb activity. 2. Through a series of molecular and biochemical experiments we will establish the mechanism by which pl05-Rb is able to mediate transcriptional repression of the human c-fos promoter.Additional genes that may be regulated by pl05-Rb will be identified and the mechanism(s) by which transcriptional repression is regulated will be determined.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA053248-01
Application #
3198041
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1990-12-12
Project End
1993-11-30
Budget Start
1990-12-12
Budget End
1991-11-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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