Prohibitin

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Prohibitin

Existing structural data : 1lu7

Properties of human protein
Mass / length primary structure 272 amino acids; 29.8 kDa
Identifier
Gene names PHB  ; PHB1
External IDs
Occurrence
Parent taxon Creature
Orthologue
human mouse
Entrez 5245 18673
Ensemble ENSG00000167085 ENSMUSG00000038845
UniProt P35232 P67778
Refseq (mRNA) NM_002634 NM_008831
Refseq (protein) NP_002625 NP_032857
Gene locus Chr 17: 44.84 - 44.85 Mb Chr 11: 95.53 - 95.54 Mb
PubMed search 5245 18673

Prohibitin ( PHB ) is a protein found in the cell membrane and the membrane of the mitochondria and is found in all tissue types. Prohibitin genes have been described in animals, fungi, plants and protozoa. The exact function of the protein is not known. Prohibitins are divided into two classes, which are called type I or type II prohibitins because of their similarities with the yeast variants of prohibitin. In all organisms examined so far, at least one prohibitin variant has always been found.

Prohibitins are evolutionarily highly conserved genes that are ubiquitously expressed . The human prohibitin gene , which is located in the BRCA1 region on chromosome 17q21, was originally thought to be a negative regulator of cell proliferation and a tumor suppressor . This antiproliferative activity is now ascribed to the 3 ' non-transcribed region of the PHB gene and not to the protein coding region. Mutations in the human PHB gene have been linked to sporadic breast cancer. Two Prohibitingen from mRNA - splice variants transcribed, differing in length of the untranslated region at the 3 'end of the gene. The longer transcript occurs mainly in proliferating tissue, which suggests that the 3 'untranslated region acts as a transactivating regulatory RNA.

Today it is assumed that prohibitins form large ring-shaped protein complexes on the inner mitochondrial membrane and are essential for the survival of multicellular organisms. The exact function of the PHB complexes is not known, but it is believed that they either act as chaperones for the respiratory chain proteins or form a kind of scaffolding for the shape of the mitochondria . It has recently been shown that prohibitins tend to be positive regulators of cell proliferation in mice and plants. In contrast, numerous publications have provided indications that prohibitin is a cell nucleus-associated repressor of the cell cycle in humans , in that it binds to the proliferation-stimulating transcription factor E2F and inhibits its activity. However, in most cases these experiments were carried out on transformed human cell lines and no indications that prohibitins have this function in normal human tissue or in other organisms have been found so far.

Individual evidence

  1. ↑ NCBI: PHB prohibitin Homo sapiens (human)

Current literature

  • McClung JK, Jupe ER, Liu XT, Dell'Orco RT: Prohibitin: potential role in senescence, development, and tumor suppression. in: Exp. Gerontol. vol. 30.2 pg. 99-124 (1996) PMID 8591812
  • Dell'Orco RT, McClung JK, Jupe ER, Liu XT: Prohibitin and the senescent phenotype. in: Exp. Gerontol. vol. 31.1-2 pg. 245-52 (1996) PMID 8706794
  • Mishra S, Murphy LC, Nyomba BL, Murphy LJ: Prohibitin: a potential target for new therapeutics. in: Trends in Molecular Medicine . vol. 11.4 pg. 192-7 (2005) PMID 15823758
  • Rajalingam K, Pack T: Ras-Raf signaling needs prohibitin. in: Cell Cycle vol. 4.11 pg. 1503-5 (2007) PMID 16294014
  • Sato T, Saito H, Swensen J, et al .: The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. in: Cancer Res . vol. 52.6 pg. 1643-6 (1992) PMID 1540973
  • Dawson SJ, White LA: Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin. In: Journal of Infection 24: 317-20 (1992) PMID 1602151
  • White JJ, Ledbetter DH, Eddy RL et al .: Assignment of the human prohibitin gene (PHB) to chromosome 17 and identification of a DNA polymorphism. in: Genomics vol. 11.1 pg. 228-30 (1992) PMID 1684951
  • Altus MS, Wood CM, Stewart DA et al .: in: Regions of evolutionary conservation between the rat and human prohibitin-encoding genes. in: Gene vol. 158.2 pg. 291-4 (1995) PMID 7607556
  • Ikonen E, Fiedler K, Parton RG, Simons K: Prohibitin, an antiproliferative protein, is localized to mitochondria. in: FEBS Lett . vol. 358.3 pg. 273-7 (1995) PMID 7843414
  • Maruyama K, Sugano S: Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. in: Gene vol. 138.1-2 pg. 171-4 (1994) PMID 8125298
  • Sato T, Sakamoto T, Takita K et al .: The human prohibitin (PHB) gene family and its somatic mutations in human tumors. in: Genomics vol. 17.3 pg. 762-4 (1993) PMID 8244394
  • Jupe ER, Liu XT, Kiehlbauch JL et al .: The 3 'untranslated region of prohibitin and cellular immortalization. in: Exp. Cell Res. vol. 224.1 pg. 128-35 (1996) PMID 8612677
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al .: Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. in: Gene vol. 200.1-2 pg. 149-56 (1997) PMID 9373149
  • Rasmussen RK, Ji H, Eddes JS et al .: Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins. in: Electrophoresis vol. 19.5 pg. 809-17 (1998) PMID 9629920
  • Wang S, Nath N, Adlam M, Chellappan S: Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. in: Oncogene vol. 18.23 pg. 3501-10 (1999) PMID 10376528
  • Wang S, Nath N, Fusaro G, Chellappan S: Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. in: Mol. Cell. Biol. Vol. 19.11 pg. 7447-60 (1999) PMID 10523633
  • Hartley JL, Temple GF, Brasch MA: DNA cloning using in vitro site-specific recombination. in: Genome Res. 10 11 pg. 1788-95 2001 PMID 11076863
  • Coates PJ, Nenutil R, McGregor A et al .: Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. in: Exp. Cell Res. 265 2 pg. 262-73 2001 PMID 11302691
  • Van Aken O, Pecenkova T, van de Cotte B et al .: Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development. in: Plant J. 52 5 pg. 850-864 2007 PMID 17883375