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Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and
M J Nuell1, D A Stewart, L Walker
1Laboratory of Molecular Genetics, National Institute on Aging, Baltimore, Maryland 21224.
Abstract:
Genes that act inside the cell to negatively regulate proliferation are of great interest because of their implications for such processes as development and cancer, but these genes have been difficult to clone. This report details the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts and HeLa cells. Microinjection of an antisense oligonucleotide stimulates entry into S phase. By sequence comparison, the prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that is vital for normal development.
Insights
Researchers cloned prohibitin, a novel mammalian antiproliferative protein. Its expression blocks cell cycle progression, suggesting a key role in regulating cell growth and development, with implications for cancer research.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Intracellular genes regulating cell proliferation are crucial for development and cancer.
- Cloning these regulatory genes has historically presented significant challenges.
Purpose of the Study:
- To detail the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein.
- To investigate the functional role of prohibitin in cell cycle regulation.
Main Methods:
- Cloning of prohibitin cDNA.
- Microinjection of synthetic prohibitin mRNA into normal fibroblasts and HeLa cells.
- Microinjection of antisense oligonucleotides.
Main Results:
- Successful cloning and analysis of prohibitin cDNA.
- Synthetic prohibitin mRNA microinjection blocked cell entry into S phase.
- Antisense oligonucleotide microinjection stimulated entry into S phase.
- Sequence comparison identified prohibitin as the mammalian analog of Drosophila's Cc gene.
Conclusions:
- Prohibitin is a novel mammalian antiproliferative protein.
- Prohibitin plays a critical role in negatively regulating cell proliferation by blocking S phase entry.
- Prohibitin's function is conserved across species, highlighting its importance in development and potentially in cancer.