Abstract

This project will investigate the molecular basis for the defects in certain inherited disorders of aging in humans: Werner syndrome and progeria. Although rare, these diseases represent an opportunity to study the aging process in general and the particular case of two human diseases which affect this process. Each of these disorders represents a single gene defect. We will apply fusion techniques to complement defects which are manifest in cells form patients with these diseases. The complemented cells will allow the identification and isolation of the gene for these diseases. As a long range goal, the function of the gene product in normal cellular function and in aging will be analyzed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG007123-06
Application #
3768188
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Duttaroy, A; Qian, J F; Smith, J S et al. (1997) Up-regulated P21CIP1 expression is part of the regulation quantitatively controlling serum deprivation-induced apoptosis. J Cell Biochem 64:434-46
Smith, J R; Nakanishi, M; Robetorye, R S et al. (1996) Studies demonstrating the complexity of regulation and action of the growth inhibitory gene SDI1. Exp Gerontol 31:327-35
Yang, L; Didenko, V V; Noda, A et al. (1995) Increased expression of p21Sdi1 in adrenocortical cells when they are placed in culture. Exp Cell Res 221:126-31
Kaul, S C; Wadhwa, R; Matsuda, Y et al. (1995) Mouse and human chromosomal assignments of mortalin, a novel member of the murine hsp70 family of proteins. FEBS Lett 361:269-72
Wadhwa, R; Pereira-Smith, O M; Reddel, R R et al. (1995) Correlation between complementation group for immortality and the cellular distribution of mortalin. Exp Cell Res 216:101-6
Nakanishi, M; Robetorye, R S; Pereira-Smith, O M et al. (1995) The C-terminal region of p21SDI1/WAF1/CIP1 is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition. J Biol Chem 270:17060-3
Hensler, P J; Pereira-Smith, O M (1995) Human replicative senescence. A molecular study. Am J Pathol 147:1-8
Khaoustov, V I; Ozer, A; Smith, J R et al. (1995) Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin. Lab Invest 73:118-27
Nakanishi, M; Robetorye, R S; Adami, G R et al. (1995) Identification of the active region of the DNA synthesis inhibitory gene p21Sdi1/CIP1/WAF1. EMBO J 14:555-63
Aggarwal, B B; Totpal, K; LaPushin, R et al. (1995) Diminished responsiveness of senescent normal human fibroblasts to TNF-dependent proliferation and interleukin production is not due to its effect on the receptors or on the activation of a nuclear factor NF-kappa B. Exp Cell Res 218:381-8

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