Prohibitin

Prohibitin, also known as PHB, is a human gene.cite web | title = Entrez Gene: PHB prohibitin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5245| accessdate = ] Prohibitin genes have been described in animals, fungi, plants and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1 or PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene. [cite journal | author=Van Aken O, Pecenkova T, van de Cotte B, "et al." |title=Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development. |journal=Plant J. |volume=52 |issue= 5 |pages= 850-864 |year= 2007 |pmid= 17883375 |doi= ] cite journal | author = Mishra S, Murphy LC, Murphy LJ | title = The Prohibitins: emerging roles in diverse functions | journal = J. Cell. Mol. Med. | volume = 10 | issue = 2 | pages = 353–63 | year = 2006 | pmid = 16796804 | doi = 10.1111/j.1582-4934.2006.tb00404.x | url = | issn = ]

Discovery

Prohibitins are evolutionarily conserved genes that are ubiquitously expressed. The human prohibitin gene, located on the BRCA1 chromosome region 17q21, was originally thought to be a negative regulator of cell proliferation and a tumor suppressor. This anti-proliferative activity was later attributed to the 3' UTR of the PHB gene, and not to the actual protein. Mutations in human PHB have been linked to sporadic breast cancer. Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.cite web | title = Entrez Gene: PHB prohibitin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5245| accessdate = ]

Function

Prohibitins may have multiple functions including:

Mitochondrial function and morphology

Prohibitins are assembled into a ring-like structure with 16–20 alternating Phb1 and Phb2 subunits in the inner mitochondrial membrane.cite journal | author = Tatsuta T, Model K, Langer T | title = Formation of membrane-bound ring complexes by prohibitins in mitochondria | journal = Mol. Biol. Cell | volume = 16 | issue = 1 | pages = 248–59 | year = 2005 | month = January | pmid = 15525670 | pmc = 539169 | doi = 10.1091/mbc.E04-09-0807 | url = | issn = ] The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiration chain proteins or a as a general structuring scaffold required for optimal mitochondrial morphology and function are suspected. Recently, prohibitins have been demonstrated to be positive, rather than negative, regulators of cell proliferation in both plants and mice.

Transcriptional modulation

Both human prohibitins have also been suggested to be localized in the nucleus and modulate transcriptional activity by interacting with various transcription factors, including nuclear receptors, either directly or indirectly. However, little evidence for nuclear targeting and transcription factor-binding of prohibitins has been found in other organism (yeast, plants, C. elegans, ...), indicating this may be a specific function in mammalian cells.cite journal | author = Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS | title = An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 12 | pages = 6947–52 | year = 1999 | month = June | pmid = 10359819 | pmc = 22022 | doi = | url = http://www.pnas.org/content/96/12/6947 | issn = ] cite journal | author = Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J, Bevan C | title = Prohibitin, a protein downregulated by androgens, represses androgen receptor activity | journal = Oncogene | volume = 26 | issue = 12 | pages = 1757–68 | year = 2007 | month = March | pmid = 16964284 | doi = 10.1038/sj.onc.1209967 | url = | issn = ] cite journal | author = Kurtev V, Margueron R, Kroboth K, Ogris E, Cavailles V, Seiser C | title = Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases | journal = J. Biol. Chem. | volume = 279 | issue = 23 | pages = 24834–43 | year = 2004 | month = June | pmid = 15140878 | doi = 10.1074/jbc.M312300200 | url = | issn = ] cite journal | author = Park SE, Xu J, Frolova A, Liao L, O'Malley BW, Katzenellenbogen BS | title = Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo | journal = Mol. Cell. Biol. | volume = 25 | issue = 5 | pages = 1989–99 | year = 2005 | month = March | pmid = 15713652 | pmc = 549370 | doi = 10.1128/MCB.25.5.1989-1999.2005 | url = | issn = ]

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=McClung JK, Jupe ER, Liu XT, Dell'Orco RT |title=Prohibitin: potential role in senescence, development, and tumor suppression. |journal=Exp. Gerontol. |volume=30 |issue= 2 |pages= 99–124 |year= 1996 |pmid= 8591812 |doi=
*cite journal | author=Dell'Orco RT, McClung JK, Jupe ER, Liu XT |title=Prohibitin and the senescent phenotype. |journal=Exp. Gerontol. |volume=31 |issue= 1-2 |pages= 245–52 |year= 1996 |pmid= 8706794 |doi=
*cite journal | author=Mishra S, Murphy LC, Nyomba BL, Murphy LJ |title=Prohibitin: a potential target for new therapeutics. |journal=Trends in molecular medicine |volume=11 |issue= 4 |pages= 192–7 |year= 2005 |pmid= 15823758 |doi= 10.1016/j.molmed.2005.02.004
*cite journal | author=Rajalingam K, Rudel T |title=Ras-Raf signaling needs prohibitin. |journal=Cell Cycle |volume=4 |issue= 11 |pages= 1503–5 |year= 2007 |pmid= 16294014 |doi=
*cite journal | author=Sato T, Saito H, Swensen J, "et al." |title=The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer. |journal=Cancer Res. |volume=52 |issue= 6 |pages= 1643–6 |year= 1992 |pmid= 1540973 |doi=
*cite journal | author=Dawson SJ, White LA |title=Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin. |journal=J. Infect. |volume=24 |issue= 3 |pages= 317–20 |year= 1992 |pmid= 1602151 |doi=
*cite journal | author=White JJ, Ledbetter DH, Eddy RL, "et al." |title=Assignment of the human prohibitin gene (PHB) to chromosome 17 and identification of a DNA polymorphism. |journal=Genomics |volume=11 |issue= 1 |pages= 228–30 |year= 1992 |pmid= 1684951 |doi=
*cite journal | author=Altus MS, Wood CM, Stewart DA, "et al." |title=Regions of evolutionary conservation between the rat and human prohibitin-encoding genes. |journal=Gene |volume=158 |issue= 2 |pages= 291–4 |year= 1995 |pmid= 7607556 |doi=
*cite journal | author=Ikonen E, Fiedler K, Parton RG, Simons K |title=Prohibitin, an antiproliferative protein, is localized to mitochondria. |journal=FEBS Lett. |volume=358 |issue= 3 |pages= 273–7 |year= 1995 |pmid= 7843414 |doi=
*cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=
*cite journal | author=Sato T, Sakamoto T, Takita K, "et al." |title=The human prohibitin (PHB) gene family and its somatic mutations in human tumors. |journal=Genomics |volume=17 |issue= 3 |pages= 762–4 |year= 1993 |pmid= 8244394 |doi=
*cite journal | author=Jupe ER, Liu XT, Kiehlbauch JL, "et al." |title=The 3' untranslated region of prohibitin and cellular immortalization. |journal=Exp. Cell Res. |volume=224 |issue= 1 |pages= 128–35 |year= 1996 |pmid= 8612677 |doi= 10.1006/excr.1996.0120
*cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, "et al." |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=
*cite journal | author=Rasmussen RK, Ji H, Eddes JS, "et al." |title=Two-dimensional electrophoretic analysis of mixed lineage kinase 2 N-terminal domain binding proteins. |journal=Electrophoresis |volume=19 |issue= 5 |pages= 809–17 |year= 1998 |pmid= 9629920 |doi= 10.1002/elps.1150190535
*cite journal | author=Wang S, Nath N, Adlam M, Chellappan S |title=Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. |journal=Oncogene |volume=18 |issue= 23 |pages= 3501–10 |year= 1999 |pmid= 10376528 |doi= 10.1038/sj.onc.1202684
*cite journal | author=Wang S, Nath N, Fusaro G, Chellappan S |title=Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. |journal=Mol. Cell. Biol. |volume=19 |issue= 11 |pages= 7447–60 |year= 1999 |pmid= 10523633 |doi=
*cite journal | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788–95 |year= 2001 |pmid= 11076863 |doi=
*cite journal | author=Coates PJ, Nenutil R, McGregor A, "et al." |title=Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. |journal=Exp. Cell Res. |volume=265 |issue= 2 |pages= 262–73 |year= 2001 |pmid= 11302691 |doi= 10.1006/excr.2001.5166
*cite journal | author=Van Aken O, Pecenkova T, van de Cotte B, "et al." |title=Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development. |journal=Plant J. |volume=52 |issue= 5 |pages= 850-864 |year= 2007 |pmid= 17883375 |doi=

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