InterPro domain: IPR000163

This entry describes proteins similar to prohibitin (a lipid raft-associated integral membrane protein). Individual proteins of the SPFH (band 7) domain superfamily may cluster to form membrane microdomains which may in turn recruit multiprotein complexes [ 1 ]. These microdomains, in addition to being stable scaffolds, may also be dynamic units with their own regulatory functions [ 2 , 3 ]. Prohibitin is a mitochondrial inner-membrane protein which may act as a chaperone for the stabilization of mitochondrial proteins. Human prohibitin forms a hetero-oligomeric complex with Bap-37 (prohibitin 2, an SPFH domain carrying homologue). This complex may protect non-assembled membrane proteins against proteolysis by the m-AAA protease [ 4 , 5 ]. Prohibitin and Bap-37 yeast homologues have been implicated in yeast longevity [ 6 ] and in the maintenance of mitochondrial morphology. Sequence comparisons suggest that the prohibitin gene is an analogue of Cc, a Drosophila melanogaster gene that is vital for normal development [ 7 ].

Genes that negatively regulate proliferation inside the cell are of considerable interest because of the implications in processes such asdevelopment and cancer [ 8 ]. Prohibitin acts as a cytoplasmic anti-proliferative protein, is widely expressed in a variety of tissues and inhibits DNA synthesis. Studies have suggested that prohibitin may be a suppressor gene and is associated with tumour development and/or progression of at least some breast cancers [ 9 ].

1. The SPFH domain-containing proteins: more than lipid raft markers. Trends Cell Biol. 17, 394-402
2. The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins. Trends Biochem. Sci. 24, 425-7
3. Scaffolding microdomains and beyond: the function of reggie/flotillin proteins. Cell. Mol. Life Sci. 62, 2228-40
4. AAA proteases of mitochondria: quality control of membrane proteins and regulatory functions during mitochondrial biogenesis. Biochem. Soc. Trans. 29, 431-6
5. Prohibitins regulate membrane protein degradation by the m-AAA protease in mitochondria. Mol. Cell. Biol. 19, 3435-42
6. Yeast replicative life span--the mitochondrial connection. FEMS Yeast Res. 5, 119-25
7. The role and therapeutic potential of prohibitin in disease. Biochim. Biophys. Acta 1813, 1137-43
8. Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells. Mol. Cell. Biol. 11, 1372-81
9. The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. Cancer Res. 52, 1643-6