Disease relevance of Phb

• Genes showing increased expression in carcinomas by cDNA microarray analysis (and further validated by immunohistochemistry and western blot analysis) include cyclin D1, PDGF-A chain, retinol binding protein 1, prohibitin and the transcription factor STAT5A [1].

High impact information on Phb

• Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells [2].
• Gonadotropin-releasing hormone attenuates pregnancy-associated thymic involution and modulates the expression of antiproliferative gene product prohibitin [3].
• In this study, we demonstrated that GnRH, GnRH-R, and PHB show characteristic polarized expression in thymocytes [3].
• In addition, GnRH and PHB were coexpressed in mature splenic T cells [3].
• Furthermore, as assessed by immunofluorescence double labeling with proliferating cell nuclear antigen, PHB was preferentially expressed in nonproliferating thymocytes [3].

Biological context of Phb

• Prohibitin content is inversely associated with cell proliferation, but it increases during granulosa cell differentiation as well as in earlier events of apoptosis in a temperature-sensitive granulosa cell line [4].
• Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival [4].
• Prohibitin is an evolutionary conserved protein that is associated with cellular differentiation, atresia, and luteolysis in the rat ovary [5].
• At a permissive temperature of 33 C, RGA-1 cells proliferate, but revert to a differentiated phenotype at a nonpermissive temperature of 39 C. Significant inductions of prohibitin mRNA and protein expression were observed in the differentiated phenotype when compared with proliferating cells [5].
• To characterize the expression of prohibitin during cell proliferation, differentiation, and cell death, we have successfully established a temperature-sensitive granulosa cell line, designated RGA-1 [5].

Anatomical context of Phb

• Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells, and the oocyte [4].
• Additionally, porcine oocytes, zygotes, and blastocyts were also immunolocalized with prohibitin antibody [4].
• Confocal and electron microscopic examinations revealed increased prohibitin localization to the mitochondria at 39 C, along with changes in mitochondrial size and shape [5].
• In addition, cell fractionation studies demonstrated that the prohibitin protein was mainly localized to the mitochondrial membrane [5].
• These studies show that the prohibitin gene is expressed differentially in testis [6].

Associations of Phb with chemical compounds

• Prohibitin was immunolocalized in rat ovarian sections probed with antibodies against either proliferating cell nuclear antigen (PCNA) or cholesterol side-chain cleavage cytochrome P450 (P450(scc)) or in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled sections [4].
• In addition, strong prohibitin expression was evident in the corpus luteum as well as in follicles undergoing atresia [7].
• Ethanol gavage significantly increased the relative abundance of prohibitin transcripts at 0.5-2 h post-PH [8].
• A transient increase in prohibitin transcripts at 0.5-1 h post-PH was found to be characteristic of glucose and nongavaged rats [8].
• The last two proteins, creatine kinase and prohibitin, increased after chronic restraint stress [9].

Other interactions of Phb

• Prohibitin and p53 transcripts were increased in relative abundance (as measured by an increase in band intensity) near the G1/S boundary (8-12 h post-PH) following both glucose and ethanol gavage [8].
• When rat prohibitin tagged with a carboxy-terminal c-Myc epitope was expressed in baby hamster kidney cells the protein was targeted to mitochondria [10].
• Expressions that decreased to less than half were observed in 20 genes, such as somatostatin and prohibitin, which prohibit cell growth [11].

Analytical, diagnostic and therapeutic context of Phb

• Western blot analyses revealed a significant increase of total PHB protein content in thymi during pregnancy [3].
• Immunocytochemistry demonstrated that prohibitin protein was expressed constitutively in adult Leydig cells and Sertoli cells at all stages [6].
• Immunoelectron microscopy revealed that prohibitin was associated with the periphery of mitochondria [10].
• In regenerating livers, prohibitin protein disappeared as early as 3 h after two-thirds hepatectomy and returned to near the original level by 24 h, while its mRNA level did not markedly vary [12].
• Western and Northern blotting techniques were used for qualitative and quantitative assessment of prohibitin expression levels within the ovary [7].

References