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Gene Review

PHB2  -  prohibitin 2

Homo sapiens

Synonyms: B-cell receptor-associated protein BAP37, BAP, BCAP37, Bap37, D-prohibitin, ...
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Disease relevance of PHB2


Psychiatry related information on PHB2

  • Ultrastructural immunohistochemistry demonstrated that HS within neurons of Alzheimer's disease (AD) brain was localized to lipofuscin granules, an aging pigment previously shown also to contain beta-amyloid protein (BAP) [6].
  • Thus, these data demonstrate that for normal children as well as for children with specific learning disabilities, attentional factors may contribute to the magnitude of the REA [7].
  • The results suggest that children with dyslexia may suffer from a primary attentional impairment in altering the REA [8].
  • The BAP has provided a review of the research evidence and clinical experience in the treatment of bipolar disorder [9].
  • We describe these entities as "tangle-associated amyloid deposits". Such BAP deposits have previously been described in some cases of AD, dementia pugilistica and LB [10].

High impact information on PHB2

  • Six patients with lymphomatous ALL had karyotypic abnormalities leading to loss of bands p21-p22 on the short arm of chromosome 9 [11].
  • On the basis of these hybrid studies the STS locus has been mapped to the distal half of the short arm (p22-pter) of the human X chromosome [12].
  • Consequently, a reduction or loss of REA function may cause overactivation of ER and increase breast cancer risk in humans [13].
  • Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland [13].
  • This study demonstrates that REA and ERalpha are coexpressed in mammary epithelial cells [13].

Chemical compound and disease context of PHB2


Biological context of PHB2

  • RNA interference-mediated knockdown of PHB2 in HeLa cells resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and fragmentation of mitochondria [19].
  • The binding of PHB1 to C3 was confirmed using a solid phase assay where the dissociation constant was approximately 90fmol/l. PHB1, but not the closely related PHB2, was able to enhance complement activation and induce lysis of sensitized sheep erythrocytes when added with normal serum but not with C3-deficient serum [20].
  • The results in the present study further characterize REA-mediated repression, and demonstrate the utility of this yeast system for dissecting molecular mechanisms involved in regulating gene transactivation by human ERalpha [21].
  • In previous work, four genes involved in mating-type determination were cloned from reference strains of Pyrenopeziza brassicae; three genes, PAD1, PMT1, and PHB1 (re-named henceforth as MAT-1-1, MAT-1-4, and MAT1-3, respectively), are encoded by the MAT-1 idiomorph, and one gene, PHB2 (re-named MAT-2), by the corresponding MAT-2 idiomorph [22].
  • Sequence homology assigns Phb1p and Phb2p to a family of proteins which also contains stomatins, HflKC, flotillins and plant defence proteins [23].

Anatomical context of PHB2

  • Here, we first demonstrated the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its nuclear targeting and showed that PHB2 is a possible molecule directly coupling nuclear-mitochondrial interaction [19].
  • In addition Phb1 and Phb2 are present in the circulation and can be internalized when added to cultured cells suggesting that the circulating prohibitins may have some regulatory role [24].
  • The prohibitins, Phb1 and Phb2 are highly conserved proteins in eukaryotic cells that are present in multiple cellular compartments [24].
  • Deletion of the Saccharomyces cerevisiae homologues, PHB1 and PHB2, results in a decreased replicative lifespan and a defect in mitochondrial membrane potential [25].
  • REA heterozygous (REA(+/-)) mutant mice exhibit faster mammary ductal elongation in virgin animals, increased lobuloalveolar development during pregnancy, and delayed mammary gland involution after weaning [13].

Associations of PHB2 with chemical compounds

  • We also found that, although PHB2 is predominantly expressed in the mitochondria of HeLa cells, it translocates to nucleus in the presence of estrogen receptor alpha and estradiol [19].
  • To define the interaction regions between ER and REA, we used glutathione S-transferase pull-down assays [26].
  • In addition, the largest decrease in free testosterone at 9 weeks was correlated with the higher values for NTX, CTX and BAP (r=-0.66, -0.68, -0.70 respectively; p< or =.01 for each of the markers) [27].
  • BAP/TFII-I, a protein implicated in transcriptional regulation, is associated with Btk in B cells and is transiently phosphorylated on tyrosine following B cell receptor engagement [28].
  • The lysis time of dialyzed normal human plasma (NHP) was longer than that of dialyzed barium citrate-adsorbed plasma (BAP) [29].

Physical interactions of PHB2


Other interactions of PHB2


Analytical, diagnostic and therapeutic context of PHB2

  • In animal experiments, intratumoral administration of Ad.TERT demonstrates potent antitumoral efficacy at least in two xenograft models (Bcap37 and BEL7404) [32].
  • Using PCR amplification, DNA cloning, sequencing, and procaryotic expression, we were able to demonstrate that HERV-K10 encodes a 73-kDa protein which was processed by a HERV-K10-encoded protease to yield proteins p22/p26, p30, and p15/16 [33].
  • Moreover, the assay detecting antibody to p22 was found to be useful for early diagnosis of HCV infection [5].
  • Immunoprecipitation experiments revealed that the p21 and p22 physically interact and form hybrid nucleocapsid structures devoid of pregenomic viral RNA [15].
  • The new ELISA test with p22 may therefore have a useful diagnostic role in acute disease [34].


  1. Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. Martini, P.G., Delage-Mourroux, R., Kraichely, D.M., Katzenellenbogen, B.S. Mol. Cell. Biol. (2000) [Pubmed]
  2. Differential immunization identifies PHB1/PHB2 as blood-borne tumor antigens. Mengwasser, J., Piau, A., Schlag, P., Sleeman, J.P. Oncogene (2004) [Pubmed]
  3. Basis of a high-throughput method for nuclear receptor ligands. Kanayama, T., Mamiya, S., Nishihara, T., Nishikawa, J. J. Biochem. (2003) [Pubmed]
  4. Rapid bone loss is associated with increased levels of biochemical markers. Ross, P.D., Knowlton, W. J. Bone Miner. Res. (1998) [Pubmed]
  5. Expression of processed core protein of hepatitis C virus in mammalian cells. Harada, S., Watanabe, Y., Takeuchi, K., Suzuki, T., Katayama, T., Takebe, Y., Saito, I., Miyamura, T. J. Virol. (1991) [Pubmed]
  6. Early accumulation of heparan sulfate in neurons and in the beta-amyloid protein-containing lesions of Alzheimer's disease and Down's syndrome. Snow, A.D., Mar, H., Nochlin, D., Sekiguchi, R.T., Kimata, K., Koike, Y., Wight, T.N. Am. J. Pathol. (1990) [Pubmed]
  7. The influence of attention on the dichotic REA with normal and learning disabled children. Obrzut, J.E., Mondor, T.A., Uecker, A. Neuropsychologia. (1993) [Pubmed]
  8. Attentional control over language lateralization in dyslexic children: deficit or delay? Kershner, J.R., Graham, N.A. Neuropsychologia. (1995) [Pubmed]
  9. The British Association for Psychopharmacology guidelines for treatment of bipolar disorder: a summary. Goodwin, G.M., Young, A.H. J. Psychopharmacol. (Oxford) (2003) [Pubmed]
  10. Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in Guamanian parkinsonism-dementia. Schwab, C., Steele, J.C., Akiyama, H., McGeer, E.G., McGeer, P.L. Acta Neuropathol. (1995) [Pubmed]
  11. Lymphoblastic leukemia with lymphomatous features associated with abnormalities of the short arm of chromosome 9. Chilcote, R.R., Brown, E., Rowley, J.D. N. Engl. J. Med. (1985) [Pubmed]
  12. Differential expression of steroid sulphatase locus on active and inactive human X chromosome. Migeon, B.R., Shapiro, L.J., Norum, R.A., Mohandas, T., Axelman, J., Dabora, R.L. Nature (1982) [Pubmed]
  13. Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland. Mussi, P., Liao, L., Park, S.E., Ciana, P., Maggi, A., Katzenellenbogen, B.S., Xu, J., O'malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  14. Expression of a repressor of estrogen receptor activity in human breast tumors: relationship to some known prognostic markers. Simon, S.L., Parkes, A., Leygue, E., Dotzlaw, H., Snell, L., Troup, S., Adeyinka, A., Watson, P.H., Murphy, L.C. Cancer Res. (2000) [Pubmed]
  15. Posttranscriptional regulation of hepatitis B virus replication by the precore protein. Scaglioni, P.P., Melegari, M., Wands, J.R. J. Virol. (1997) [Pubmed]
  16. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study). Woelk, H., Lehrl, S., Bitsch, R., Köpcke, W. Alcohol Alcohol. (1998) [Pubmed]
  17. Species identification by genotyping and determination of antibiotic resistance in Campylobacter jejuni and Campylobacter coli from humans and chickens in Sweden. Rönner, A.C., Engvall, E.O., Andersson, L., Kaijser, B. Int. J. Food Microbiol. (2004) [Pubmed]
  18. Multiple myeloma resistant to melphalan: treatment with doxorubicin, cyclophosphamide, carmustine (BCNU), and prednisone. Kyle, R.A., Pajak, T.F., Henderson, E.S., Nawabi, I.U., Brunner, K., Henry, P.H., McIntyre, O.R., Holland, J.F. Cancer treatment reports. (1982) [Pubmed]
  19. Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2. Kasashima, K., Ohta, E., Kagawa, Y., Endo, H. J. Biol. Chem. (2006) [Pubmed]
  20. Prohibitin binds to C3 and enhances complement activation. Mishra, S., Moulik, S., Murphy, L.J. Mol. Immunol. (2007) [Pubmed]
  21. Regulation of human estrogen receptor alpha-mediated gene transactivation in Saccharomyces cerevisiae by human coactivator and corepressor proteins. Bitter, G.A. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  22. Intra-specific and inter-specific conservation of mating-type genes from the discomycete plant-pathogenic fungi Pyrenopeziza brassicae and Tapesia yallundae. Singh, G., Dyer, P.S., Ashby, A.M. Curr. Genet. (1999) [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. The Prohibitins: emerging roles in diverse functions. Mishra, S., Murphy, L.C., Murphy, L.J. J. Cell. Mol. Med. (2006) [Pubmed]
  25. The prohibitin family of mitochondrial proteins regulate replicative lifespan. Coates, P.J., Jamieson, D.J., Smart, K., Prescott, A.R., Hall, P.A. Curr. Biol. (1997) [Pubmed]
  26. Analysis of estrogen receptor interaction with a repressor of estrogen receptor activity (REA) and the regulation of estrogen receptor transcriptional activity by REA. Delage-Mourroux, R., Martini, P.G., Choi, I., Kraichely, D.M., Hoeksema, J., Katzenellenbogen, B.S. J. Biol. Chem. (2000) [Pubmed]
  27. The effect of short-term treatment with micronized estradiol on bone turnover and gonadotrophins in older men. Taxel, P., Kennedy, D., Fall, P., Willard, A., Shoukri, K., Clive, J., Raisz, L.G. Endocr. Res. (2000) [Pubmed]
  28. Identification of phosphorylation sites for Bruton's tyrosine kinase within the transcriptional regulator BAP/TFII-I. Egloff, A.M., Desiderio, S. J. Biol. Chem. (2001) [Pubmed]
  29. The effect of activated protein C on fibrinolysis in cell-free plasma can be attributed specifically to attenuation of prothrombin activation. Bajzar, L., Nesheim, M. J. Biol. Chem. (1993) [Pubmed]
  30. HSF1 blockade-induced tumor thermotolerance abolishment is mediated by JNK-dependent caspase-3 activation. Wang, J.H., Yao, M.Z., Zhang, Z.L., Zhang, Y.H., Wang, Y.G., Liu, X.Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  31. Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity. Han, M.Y., Zheng, S., Yu, J.M., Peng, J.P., Guo, Q.S., Wang, J.L. J. Zhejiang Univ. Sci. (2004) [Pubmed]
  32. A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent. Zou, W., Luo, C., Zhang, Z., Liu, J., Gu, J., Pei, Z., Qian, C., Liu, X. Oncogene (2004) [Pubmed]
  33. Human endogenous retrovirus K10: expression of Gag protein and detection of antibodies in patients with seminomas. Sauter, M., Schommer, S., Kremmer, E., Remberger, K., Dölken, G., Lemm, I., Buck, M., Best, B., Neumann-Haefelin, D., Mueller-Lantzsch, N. J. Virol. (1995) [Pubmed]
  34. Serological response and detection of viraemia in acute hepatitis C virus infection. Dourakis, S., Brown, J., Kumar, U., Karayiannis, P., Kernoff, P., Chiba, J., Ohba, H., Miyamura, T., Saito, I., Monjardino, J. J. Hepatol. (1992) [Pubmed]
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