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Gene Review

PHB  -  prohibitin

Homo sapiens

Synonyms: HEL-215, HEL-S-54e, PHB1, Prohibitin
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Disease relevance of PHB

  • We recently observed that prohibitin, a potential tumor suppressor protein, binds to the retinoblastoma (Rb) protein and represses E2F transcriptional activity [1].
  • Here we show that prohibitin is predominantly nuclear in two breast cancer cell lines where it co-localizes with E2F1 and p53 [2].
  • Surprisingly, prohibitin-mediated repression of E2F could not be reversed by adenovirus E1A protein [3].
  • Prohibitin 1 activation seems to be an early event, whereas c-Met overexpression may be important for the progression of cervical adenocarcinomas [4].
  • The diverse array of functions of PHB, together with the emerging evidence that its function can be modulated specifically in certain tissues, suggest that targeting PHB would be a useful therapeutic approach for the treatment of variety of disease states, including inflammation, obesity and cancer [5].

Psychiatry related information on PHB


High impact information on PHB


Chemical compound and disease context of PHB


Biological context of PHB


Anatomical context of PHB


Associations of PHB with chemical compounds


Physical interactions of PHB

  • The data presented here also show that prohibitin is capable of physically interacting with p53 in vivo and in vitro [2].
  • Here we show that the E2F1 binding domain of prohibitin has the potential to fold into a coiled-coil structure [22].
  • On the basis of its native molecular weight, the PHB-complex should contain 12-14 copies of both Phblp and Phb2p [23].
  • We have employed a yeast two-hybrid screen to identify other interacting proteins and have identified alpha-actinin and annexin A2 as binding partners for prohibitin and prohibitone [24].
  • Confirming this, prohibitin was found to physically interact with CRM-1, and this interaction was significantly higher in transformed cells [18].

Regulatory relationships of PHB

  • Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter [16].
  • Prohibitin appears to induce p53-mediated transcription by enhancing its recruitment to promoters, as detected by chromatin immunoprecipitation assays [2].
  • One of the proteins that was identified among other PDGF-regulated molecules was prohibitin, a potential tumour suppressor previously implicated in cell cycle regulation and protection of mitochondrial proteins from degradation [25].

Other interactions of PHB


Analytical, diagnostic and therapeutic context of PHB


  1. Rb and prohibitin target distinct regions of E2F1 for repression and respond to different upstream signals. Wang, S., Nath, N., Fusaro, G., Chellappan, S. Mol. Cell. Biol. (1999) [Pubmed]
  2. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. Fusaro, G., Dasgupta, P., Rastogi, S., Joshi, B., Chellappan, S. J. Biol. Chem. (2003) [Pubmed]
  3. Prohibitin, a potential tumor suppressor, interacts with RB and regulates E2F function. Wang, S., Nath, N., Adlam, M., Chellappan, S. Oncogene (1999) [Pubmed]
  4. The significance of prohibitin and c-Met/hepatocyte growth factor receptor in the progression of cervical adenocarcinoma. Tsai, H.W., Chow, N.H., Lin, C.P., Chan, S.H., Chou, C.Y., Ho, C.L. Hum. Pathol. (2006) [Pubmed]
  5. Prohibitin: a potential target for new therapeutics. Mishra, S., Murphy, L.C., Nyomba, B.L., Murphy, L.J. Trends in molecular medicine. (2005) [Pubmed]
  6. Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease. Ferrer, I., Perez, E., Dalfó, E., Barrachina, M. Neurosci. Lett. (2007) [Pubmed]
  7. Prohibitin is required for Ras-induced Raf-MEK-ERK activation and epithelial cell migration. Rajalingam, K., Wunder, C., Brinkmann, V., Churin, Y., Hekman, M., Sievers, C., Rapp, U.R., Rudel, T. Nat. Cell Biol. (2005) [Pubmed]
  8. Prohibitin 3' untranslated region polymorphism and breast cancer risk in Australian women. Spurdle, A.B., Hopper, J.L., Chen, X., McCredie, M.R., Giles, G.G., Newman, B., Chenevix-Trench, G. Lancet (2002) [Pubmed]
  9. Single nucleotide polymorphism in prohibitin 39 untranslated region and breast-cancer susceptibility. Jupe, E.R., Badgett, A.A., Neas, B.R., Craft, M.A., Mitchell, D.S., Resta, R., Mulvihill, J.J., Aston, C.E., Thompson, L.F. Lancet (2001) [Pubmed]
  10. Structure and enzymatic degradation of poly(3-hydroxybutyrate) copolymer single crystals with an extracellular PHB depolymerase from Alcaligenes faecalis T1. Iwata, T., Doi, Y., Nakayama, S., Sasatsuki, H., Teramachi, S. Int. J. Biol. Macromol. (1999) [Pubmed]
  11. Photosynthetic accumulation of poly-(hydroxybutyrate) by cyanobacteria--the metabolism and potential for CO2 recycling. Asada, Y., Miyake, M., Miyake, J., Kurane, R., Tokiwa, Y. Int. J. Biol. Macromol. (1999) [Pubmed]
  12. Incorporation of polyethylene glycol in polyhydroxyalkanoic acids accumulated by Azotobacter chroococcum MAL-201. Saha, S.P., Patra, A., Paul, A.K. J. Ind. Microbiol. Biotechnol. (2006) [Pubmed]
  13. Vi polysaccharide of Salmonella typhi targets the prohibitin family of molecules in intestinal epithelial cells and suppresses early inflammatory responses. Sharma, A., Qadri, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  14. Prohibitin and Cofilin Are Intracellular Effectors of Transforming Growth Factor {beta} Signaling in Human Prostate Cancer Cells. Zhu, B., Fukada, K., Zhu, H., Kyprianou, N. Cancer Res. (2006) [Pubmed]
  15. Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression. Wang, S., Fusaro, G., Padmanabhan, J., Chellappan, S.P. Oncogene (2002) [Pubmed]
  16. Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites. Joshi, B., Rastogi, S., Morris, M., Carastro, L.M., DeCook, C., Seto, E., Chellappan, S.P. Biochem. J. (2007) [Pubmed]
  17. BRG1/BRM and prohibitin are required for growth suppression by estrogen antagonists. Wang, S., Zhang, B., Faller, D.V. EMBO J. (2004) [Pubmed]
  18. Camptothecin induces nuclear export of prohibitin preferentially in transformed cells through a CRM-1-dependent mechanism. Rastogi, S., Joshi, B., Fusaro, G., Chellappan, S. J. Biol. Chem. (2006) [Pubmed]
  19. Prohibitin binds to C3 and enhances complement activation. Mishra, S., Moulik, S., Murphy, L.J. Mol. Immunol. (2007) [Pubmed]
  20. Inaugural Article: Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Huber, T.B., Schermer, B., M??ller, R.U., H??hne, M., Bartram, M., Calixto, A., Hagmann, H., Reinhardt, C., Koos, F., Kunzelmann, K., Shirokova, E., Krautwurst, D., Harteneck, C., Simons, M., Pavenst??dt, H., Kerjaschki, D., Thiele, C., Walz, G., Chalfie, M., Benzing, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  21. Comparative effects of cetaben (PHB) and dichlormethylene diphosphonate (Cl2MDP) on the development of atherosclerosis in the cynomolgus monkey. Hollander, W., Prusty, S., Nagraj, S., Kirkpatrick, B., Paddock, J., Colombo, M. Atherosclerosis (1978) [Pubmed]
  22. A putative coiled-coil domain of prohibitin is sufficient to repress E2F1-mediated transcription and induce apoptosis. Joshi, B., Ko, D., Ordonez-Ercan, D., Chellappan, S.P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease. Nijtmans, L.G., Artal, S.M., Grivell, L.A., Coates, P.J. Cell. Mol. Life Sci. (2002) [Pubmed]
  24. Prohibitin and prohibitone are contained in high-molecular weight complexes and interact with alpha-actinin and annexin A2. Bacher, S., Achatz, G., Schmitz, M.L., Lamers, M.C. Biochimie (2002) [Pubmed]
  25. Identification of growth factor-regulated proteins using 2D electrophoresis and mass spectrometry. Saridaki, A., Panayotou, G. Growth Factors (2005) [Pubmed]
  26. The human prohibitin (PHB) gene family and its somatic mutations in human tumors. Sato, T., Sakamoto, T., Takita, K., Saito, H., Okui, K., Nakamura, Y. Genomics (1993) [Pubmed]
  27. Regions of evolutionary conservation between the rat and human prohibitin-encoding genes. Altus, M.S., Wood, C.M., Stewart, D.A., Roskams, A.J., Friedman, V., Henderson, T., Owens, G.A., Danner, D.B., Jupe, E.R., Dell'Orco, R.T. Gene (1995) [Pubmed]
  28. Tumor suppression by the prohibitin gene 3'untranslated region RNA in human breast cancer. Manjeshwar, S., Branam, D.E., Lerner, M.R., Brackett, D.J., Jupe, E.R. Cancer Res. (2003) [Pubmed]
  29. The 3' untranslated region of prohibitin and cellular immortalization. Jupe, E.R., Liu, X.T., Kiehlbauch, J.L., McClung, J.K., Dell'Orco, R.T. Exp. Cell Res. (1996) [Pubmed]
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