In earlier work, we isolated a cDNA for the protein prohibitin based on its preferential expression in nondividing liver and the ability of its mRNA to block normal fibroblasts and cancer cells from entering S phase. Prohibitin was shown to be expressed in a wide range of cells; in fibroblasts, it was expressed at a high level in G1 and a low level in S. Prohibitin was shown to be highly conserved between rats and fruit flies. During the last year we have found that: 1) rat and human proteins are identical; 2) Drosophilia prohibitin mRNA shuts off human cells; and 3) human and yeast proteins are 53% identical. We have also observed a possible role for prohibition in meiosis: 1) heterozygote mutants in yeast prohibitin block sporulation; and 2) testicular cells have prohibitin mRNAs not seen in other tissues. Some other findings suggest areas for further research: 1) an antibody has been developed which shows that prohibitin levels decrease as cells become contact inhibited; 2) prohibitin has been found to be negatively regulated by protein kinase A and positively regulated by protein kinase C; and 3) the chromosomal location of the human prohibitin gene has been established, which may be helpful in determining if prohibitin is a tumor suppressor gene.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000705-06
Application #
3802304
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Sharov, Alexei A; Falco, Geppino; Piao, Yulan et al. (2008) Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary. BMC Biol 6:24
Zahn, Jacob M; Poosala, Suresh; Owen, Art B et al. (2007) AGEMAP: a gene expression database for aging in mice. PLoS Genet 3:e201