Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033694-10
Application #
3283615
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

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
Dews, M; Prisco, M; Peruzzi, F et al. (2000) Domains of the insulin-like growth factor I receptor required for the activation of extracellular signal-regulated kinases. Endocrinology 141:1289-300
Gatzka, M; Prisco, M; Baserga, R (2000) Stabilization of the Ras oncoprotein by the insulin-like growth factor 1 receptor during anchorage-independent growth. Cancer Res 60:4222-30
Valentinis, B; Romano, G; Peruzzi, F et al. (1999) Growth and differentiation signals by the insulin-like growth factor 1 receptor in hemopoietic cells are mediated through different pathways. J Biol Chem 274:12423-30
Reiss, K; Yumet, G; Shan, S et al. (1999) Synthetic peptide sequence from the C-terminus of the insulin-like growth factor-I receptor that induces apoptosis and inhibition of tumor growth. J Cell Physiol 181:124-35
Morrione, A; Plant, P; Valentinis, B et al. (1999) mGrb10 interacts with Nedd4. J Biol Chem 274:24094-9
Baserga, R; Morrione, A (1999) Differentiation and malignant transformation: two roads diverged in a wood. J Cell Biochem Suppl 32-33:68-75
Prisco, M; Romano, G; Peruzzi, F et al. (1999) Insulin and IGF-I receptors signaling in protection from apoptosis. Horm Metab Res 31:80-9
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

Showing the most recent 10 out of 78 publications