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Available structures
PDBOrtholog search: PDBe RCSB
AliasesPHB1, HEL-215, HEL-S-54e, prohibitin, prohibitin 1, PHB
External IDsOMIM: 176705 MGI: 97572 HomoloGene: 1980 GeneCards: PHB1
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 17: 49.4 – 49.41 MbChr 11: 95.56 – 95.57 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Prohibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene.[5] 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.[6][7]


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. However, over-expression of PHB has been associated with a reduction in the androgen receptor activity and a reduction in PSA gene expression resulting in a decrease of androgen-dependent growth of cancerous prostate cells.[8] 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.[5]


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.[9] 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

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.[10][11][12][13]

Clinical significance

Human prohibitin 1 has some activity as a virus receptor protein, having been identified as a receptor for Chikungunya Virus (CHIKV)[14] and Dengue Virus 2 (DENV-2).[15] Little else is known about the activity of the prohibitins in viral pathogenesis.


Prohibitin has been shown to interact with:

Drugs that bind to prohibitin


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167085 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038845 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: PHB prohibitin".
  6. ^ Van Aken O, Pecenková T, van de Cotte B, De Rycke R, Eeckhout D, Fromm H, De Jaeger G, Witters E, Beemster GT, Inzé D, Van Breusegem F (Dec 2007). "Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development". The Plant Journal. 52 (5): 850–64. doi:10.1111/j.1365-313X.2007.03276.x. PMID 17883375.
  7. ^ Mishra S, Murphy LC, Murphy LJ (2006). "The Prohibitins: emerging roles in diverse functions". Journal of Cellular and Molecular Medicine. 10 (2): 353–63. doi:10.1111/j.1582-4934.2006.tb00404.x. PMC 3933126. PMID 16796804.
  8. ^ Dart, D Alwyn (2009). "Manipulating prohibitin levels provides evidence for an in vivo role in androgen regulation of prostate tumours". Endocrine-Related Cancer. 16 (4): 1157–1169. doi:10.1677/ERC-09-0028. PMC 2782800. PMID 19635783.
  9. ^ Tatsuta T, Model K, Langer T (Jan 2005). "Formation of membrane-bound ring complexes by prohibitins in mitochondria". Molecular Biology of the Cell. 16 (1): 248–59. doi:10.1091/mbc.E04-09-0807. PMC 539169. PMID 15525670.
  10. ^ Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS (Jun 1999). "An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens". Proceedings of the National Academy of Sciences of the United States of America. 96 (12): 6947–52. Bibcode:1999PNAS...96.6947M. doi:10.1073/pnas.96.12.6947. PMC 22022. PMID 10359819.
  11. ^ Gamble SC, Chotai D, Odontiadis M, Dart DA, Brooke GN, Powell SM, Reebye V, Varela-Carver A, Kawano Y, Waxman J, Bevan CL (Mar 2007). "Prohibitin, a protein downregulated by androgens, represses androgen receptor activity". Oncogene. 26 (12): 1757–68. doi:10.1038/sj.onc.1209967. PMID 16964284. S2CID 9592990.
  12. ^ Kurtev V, Margueron R, Kroboth K, Ogris E, Cavailles V, Seiser C (Jun 2004). "Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases". The Journal of Biological Chemistry. 279 (23): 24834–43. doi:10.1074/jbc.M312300200. PMID 15140878.
  13. ^ Park SE, Xu J, Frolova A, Liao L, O'Malley BW, Katzenellenbogen BS (Mar 2005). "Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo". Molecular and Cellular Biology. 25 (5): 1989–99. doi:10.1128/MCB.25.5.1989-1999.2005. PMC 549370. PMID 15713652.
  14. ^ 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 (Nov 2012). "Identification of prohibitin as a Chikungunya virus receptor protein". Journal of Medical Virology. 84 (11): 1757–70. doi:10.1002/jmv.23403. PMID 22997079. S2CID 22172257.
  15. ^ Kuadkitkan A, Wikan N, Fongsaran C, Smith DR (Oct 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.
  16. ^ 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.
  17. ^ 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". Molecular and Cellular Biology. 19 (11): 7447–60. doi:10.1128/mcb.19.11.7447. PMC 84738. PMID 10523633.
  18. ^ 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". Biochemical and Biophysical Research Communications. 312 (2): 459–66. doi:10.1016/j.bbrc.2003.10.148. PMID 14637159.
  19. ^ 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". The Journal of Biological Chemistry. 278 (48): 47853–61. doi:10.1074/jbc.M305171200. PMID 14500729.
  20. ^ 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". The EMBO Journal. 21 (12): 3019–28. doi:10.1093/emboj/cdf302. PMC 126057. PMID 12065415.
  21. ^ 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.
  22. ^ 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.
  23. ^ Sato S, Murata A, Orihara T, Shirakawa T, Suenaga K, Kigoshi H, Uesugi M (Jan 2011). "Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin". Chemistry & Biology. 18 (1): 131–9. doi:10.1016/j.chembiol.2010.10.017. PMID 21276946.
  24. ^ Pérez-Perarnau A, Preciado S, Palmeri CM, Moncunill-Massaguer C, Iglesias-Serret D, González-Gironès DM, Miguel M, Karasawa S, Sakamoto S, Cosialls AM, Rubio-Patiño C, Saura-Esteller J, Ramón R, Caja L, Fabregat I, Pons G, Handa H, Albericio F, Gil J, Lavilla R (Sep 2014). "A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins". Angewandte Chemie. 53 (38): 10150–4. doi:10.1002/anie.201405758. PMID 25196378.
  25. ^ Moncunill-Massaguer C, Saura-Esteller J, Pérez-Perarnau A, Palmeri CM, Núñez-Vázquez S, Cosialls AM, González-Gironès DM, Pomares H, Korwitz A, Preciado S, Albericio F, Lavilla R, Pons G, Langer T, Iglesias-Serret D, Gil J (Dec 2015). "A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation". Oncotarget. 6 (39): 41750–65. doi:10.18632/oncotarget.6154. PMC 4747186. PMID 26497683.
  26. ^ Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller WW, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer PH, Li-Weber M (Sep 2012). "The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2". Chemistry & Biology. 19 (9): 1093–104. doi:10.1016/j.chembiol.2012.07.012. PMID 22999878.

Further reading