The Proliferating Cell Nuclear Antigen (PCNA), as the co-factor of DNA polymerase delta, is absolutely required for DNA replication and cellular proliferation. The expression of PCNA, like the expression of other genes coding for proteins of the DNA synthesizing apparatus, increases sharply at the G1/S boundary in Go cells stimulated by serum or growth factors. The co-ordinate expression of these genes indicates that, although some diversity may be present, some common mechanism(s) must also be operative in their near-simultaneous activation. By investigating the regulation of PCNA expression, we hope to identify regulatory proteins that not only modulate PCNA expression (in itself of considerable interest) but may be also involved in the regulation of other G1/S boundary genes. Since the G1/S transition is one of the critical steps in the control of cell proliferation, the identification of regulatory proteins at this point is of major significance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033694-12
Application #
2177098
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Valentinis, B; Navarro, M; Zanocco-Marani, T et al. (2000) Insulin receptor substrate-1, p70S6K, and cell size in transformation and differentiation of hemopoietic cells. J Biol Chem 275:25451-9
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Morrione, A; Plant, P; Valentinis, B et al. (1999) mGrb10 interacts with Nedd4. J Biol Chem 274:24094-9
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Peruzzi, F; Prisco, M; Dews, M et al. (1999) Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol Cell Biol 19:7203-15
Valentinis, B; Morrione, A; Peruzzi, F et al. (1999) Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion. Oncogene 18:1827-36

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