During the cell cycle, growth in size and cell DNA replication are coordinated. However, recent evidence has shown that the two processes can be dissociated and are under different control mechanisms. Preliminary work suggests that the p53 protein, which plays a role in the proliferation of mammalian cells, may also regulate the amount of total cellular RNA. We propose to investigate the role of the p53 protein in growth in size and cell DNA replication by using the system of mitogen-stimulated lymphocytes. This system is based on the observation that T-lymphocytes grow in size but do not enter S phase when exposed to phytohemagglutin, but do enter S phase when macrophages (or Interleukin-2) are added to the phytohemagglutinin stimulated populations. By using this system, a monoclonal antibody against the p53 protein, a cDNA probe of p53 mRNA, and microinjection, we intend to further define the role of the p53 protein in cell proliferation. In turn, these studies should establish a better basis for future investigations dealing with the mechanism by which the p53 protein regulates the progression of cells through the cell cycle.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033694-02
Application #
3283610
Study Section
Pathology B Study Section (PTHB)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Temple University
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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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

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