Disease relevance of PHB2

• We isolated PTalpha, known to be a chromatin-remodeling protein associated with cell proliferation, using REA as bait in a yeast two-hybrid screen with a cDNA library from MCF-7 human breast cancer cells [1].
• Using this method, we have identified PHB1 and PHB2, proteins thought to function as mitochondrial chaperones and transcriptional regulators, as antigens released from colorectal tumors in vivo [2].
• We used human TIF2 as a coactivator including LXXLL motifs expressed in Escherichia coli as a fusion protein with BAP and nuclear receptor LBD expressed in E. coli as a fusion protein with GST [3].
• Two markers of bone formation, serum bone alkaline phosphatase (Alkphase-B; BAP) and osteocalcin (NovoCalcin; OC), and two markers of bone resorption, urinary creatinine-corrected free deoxypyridinoline (Pyrilinks-D; DPD) and free pyridinolines (Pyrilinks; PYD), were measured [4].
• These results suggested that the p22 protein is the nucleocapsid (core) protein of HCV [5].

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

• The expression of a specific repressor of estrogen receptor activity (REA) was investigated by a semiquantitative reverse transcription-PCR assay in 40 human breast tumor biopsy samples with respect to steroid hormone receptor status and other known prognostic variables [14].
• By sucrose gradient sedimentation analysis, we determined that expression of p22 leads to the formation of nucleocapsids similar to those made with wild-type p21 core protein [15].
• Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study) [16].
• One aim with our present study was to identify the species Campylobacter jejuni and Campylobacter coli strains from humans and chickens using a polymerase chain reaction/restriction enzyme analysis (PCR/REA) method, as well as traditional hippurate hydrolysis test [17].
• Sixty-five patients with multiple myeloma resistant to melphalan were randomized to receive cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP) (30 patients) or carmustine (BCNU), doxorubicin, and prednisone (BAP) (35 patients) [18].

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

• On the basis of its native molecular weight, the PHB-complex should contain 12-14 copies of both Phblp and Phb2p [23].

Other interactions of PHB2

• Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2 [19].
• We previously blocked the heat shock transcription factor 1 function with a dominant-negative mutant (mHSF1) in breast cancer cell line Bcap37, and found that mHSF1 sensitizes Bcap37 cells to hyperthermia by promoting the apoptotic process [30].
• The biological expression of rhIL-18 was tested by RT-PCR and ELISA method; nude mice were injected with Bcap37 cell with or without the hIL-18 gene [31].

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].

References