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Available structures
PDB Ortholog search: PDBe, RCSB
Symbols PHB ; HEL-215; HEL-S-54e; PHB1
External IDs OMIM176705 MGI97572 HomoloGene1980 GeneCards: PHB Gene
RNA expression pattern
PBB GE PHB 200658 s at tn.png
PBB GE PHB 200659 s at tn.png
More reference expression data
Species Human Mouse
Entrez 5245 18673
Ensembl ENSG00000167085 ENSMUSG00000038845
UniProt P35232 P67778
RefSeq (mRNA) NM_001281496 NM_008831
RefSeq (protein) NP_001268425 NP_032857
Location (UCSC) Chr 17:
49.4 – 49.41 Mb
Chr 11:
95.67 – 95.68 Mb
PubMed search [1] [2]

Prohibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene.[1] The Phb gene has also 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 and PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene.[2][3]


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.[1]


Prohibitins may have multiple functions including:

Mitochondrial function and morphology[edit]

Prohibitins are assembled into a ring-like structure with 16–20 alternating Phb1 and Phb2 subunits in the inner mitochondrial membrane.[4] The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiration chain proteins or 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[edit]

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, etc.), indicating that this may be a specific function in mammalian cells.[5][6][7][8]

Clinical significance[edit]

Human prohibitin 1 has some activity as a virus receptor protein, having been identified as a receptor for Chikungunya Virus (CHIKV)[9] and Dengue Virus 2 (DENV-2).[10] Little else is known about the activity of the prohibitins in viral pathogenesis.


Prohibitin has been shown to interact with:


  1. ^ a b "Entrez Gene: PHB prohibitin". 
  2. ^ Van Aken O, Pecenkova T, van de Cotte B, et al. (2007). "Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development". Plant J. 52 (5): 850–864. doi:10.1111/j.1365-313X.2007.03276.x. PMID 17883375. 
  3. ^ Mishra S, Murphy LC, Murphy LJ (2006). "The Prohibitins: emerging roles in diverse functions". J. Cell. Mol. Med. 10 (2): 353–63. doi:10.1111/j.1582-4934.2006.tb00404.x. PMID 16796804. 
  4. ^ Tatsuta T, Model K, Langer T (January 2005). "Formation of Membrane-bound Ring Complexes by Prohibitins in Mitochondria". Mol. Biol. Cell 16 (1): 248–59. doi:10.1091/mbc.E04-09-0807. PMC 539169. PMID 15525670. 
  5. ^ Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS (June 1999). "An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens". Proc. Natl. Acad. Sci. U.S.A. 96 (12): 6947–52. doi:10.1073/pnas.96.12.6947. PMC 22022. PMID 10359819. 
  6. ^ Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J, Bevan C (March 2007). "Prohibitin, a protein downregulated by androgens, represses androgen receptor activity". Oncogene 26 (12): 1757–68. doi:10.1038/sj.onc.1209967. PMID 16964284. 
  7. ^ Kurtev V, Margueron R, Kroboth K, Ogris E, Cavailles V, Seiser C (June 2004). "Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases". J. Biol. Chem. 279 (23): 24834–43. doi:10.1074/jbc.M312300200. PMID 15140878. 
  8. ^ Park SE, Xu J, Frolova A, Liao L, O'Malley BW, Katzenellenbogen BS (March 2005). "Genetic Deletion of the Repressor of Estrogen Receptor Activity (REA) Enhances the Response to Estrogen in Target Tissues In Vivo". Mol. Cell. Biol. 25 (5): 1989–99. doi:10.1128/MCB.25.5.1989-1999.2005. PMC 549370. PMID 15713652. 
  9. ^ Wintachai P, Wikan N, Kuadkitkan A, Jaimipuk T, Ubol S, Pulmanausahakul R, Auewarakul P, Kasinrerk W, Weng WY, Panyasrivanit M, Paemanee A, Kittisenachai S, Roytrakul S, Smith DR (2012). "Identification of prohibitin as a Chikungunya virus receptor protein". J. Med. Virol. 84 (11): 1757–70. doi:10.1002/jmv.23403. PMID 22997079. 
  10. ^ Kuadkitkan A, Wikan N, Fongsaran C, Smith DR (2010). "Identification and characterization of prohibitin as a receptor protein mediating DENV-2 entry into insect cells". Virology 406 (1): 149–61. doi:10.1016/j.virol.2010.07.015. PMID 20674955. 
  11. ^ Bacher S, Achatz G, Schmitz ML, Lamers MC (Dec 2002). "Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2". Biochimie 84 (12): 1207–20. doi:10.1016/s0300-9084(02)00027-5. PMID 12628297. 
  12. ^ a b c Wang S, Nath N, Fusaro G, Chellappan S (Nov 1999). "Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals". Mol. Cell. Biol. 19 (11): 7447–60. PMC 84738. PMID 10523633. 
  13. ^ a b Joshi B, Ko D, Ordonez-Ercan D, Chellappan SP (Dec 2003). "A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis". Biochem. Biophys. Res. Commun. 312 (2): 459–66. doi:10.1016/j.bbrc.2003.10.148. PMID 14637159. 
  14. ^ a b Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S (Nov 2003). "Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling". J. Biol. Chem. 278 (48): 47853–61. doi:10.1074/jbc.M305171200. PMID 14500729. 
  15. ^ a b c Wang S, Zhang B, Faller DV (Jun 2002). "Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth". EMBO J. 21 (12): 3019–28. doi:10.1093/emboj/cdf302. PMC 126057. PMID 12065415. 
  16. ^ Wang S, Fusaro G, Padmanabhan J, Chellappan SP (Dec 2002). "Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression". Oncogene 21 (55): 8388–96. doi:10.1038/sj.onc.1205944. PMID 12466959. 
  17. ^ a b c Wang S, Nath N, Adlam M, Chellappan S (Jun 1999). "Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function". Oncogene 18 (23): 3501–10. doi:10.1038/sj.onc.1202684. PMID 10376528. 

Further reading[edit]