Disease relevance of Phb2

• Consequently, a reduction or loss of REA function may cause overactivation of ER and increase breast cancer risk in humans [1].
• REA mRNA and protein levels in uteri of heterozygous animals were half that of the wild type, and studies with heterozygous animals revealed a greater uterine weight gain and epithelial hyperproliferation in response to estradiol (E2) and a substantially greater stimulation by E2 of a number of estrogen up-regulated genes in the uterus [2].
• To test whether a wild-type lapine rotavirus strain BAP (BAPwt) isolated from diarrheic rabbits would cause disease on passage in rabbits, 1-, 2-, 10-, and 16-week-old rabbits were orally inoculated with BAPwt, its tissue culture-adapted counterpart strain (BAP-2), tissue culture-adapted lapine strain ALA, or PBS [3].
• Bap, a Staphylococcus aureus surface protein involved in biofilm formation [4].
• This locus (bap [for biofilm associated protein]) encodes a novel cell wall associated protein of 2,276 amino acids (Bap), which shows global organizational similarities to surface proteins of gram-negative (Pseudomonas aeruginosa and Salmonella enterica serovar Typhi) and gram-positive (Enteroccocus faecalis) microorganisms [4].

Psychiatry related information on Phb2

• Amnesia was induced in mice by intracerebroventricular (i.c.v.) injection of beta-amyloid 1-42 fragment (BAP 1-42; 400 pmol/mouse) or of galanin (GAL) 1-29 (3 mug/mouse) [5].

High impact information on Phb2

• Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland [1].
• This study demonstrates that REA and ERalpha are coexpressed in mammary epithelial cells [1].
• Our results indicate that REA is a physiological modulator of ER function in the mammary gland and that its correct gene dosage is required for maintenance of normal ER activity and normal mammary gland development [1].
• Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo [2].
• Even more dramatic in REA heterozygous animals was the loss of down regulation by E2 of genes in the uterus that are normally repressed by estrogen in wild-type animals [2].

Biological context of Phb2

• Decreasing the intracellular level of REA by using small interfering RNA knockdown or antisense RNA approaches in cells in culture resulted in a significant increase in the level of up-regulation of estrogen-stimulated genes [2].
• These residues, Tyr248, Tyr357, and Tyr462, were also found to be the major sites for Btk-dependent phosphorylation of BAP/TFII-I in vivo [6].
• Here we report that retrovirus-mediated transfer of mHSF1 led to massive cell death of Bcap37 after hyperthermia. mHSF1 sensitized Bcap37 cells to hyperthermia by promoting apoptosis induced by heat shock [7].
• Alpha-Amanitin showed no significant binding capacity to calf thymus DNA, but aucubin was found to interact with DNA, and the apparent binding constant (Kapp) and apparent number of binding sites per DNA phosphate (Bapp) were 0.45 x 10(4) M(-1) and 1.25, respectively [8].

Anatomical context of Phb2

• 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 [1].
• We found that repressor of estrogen receptor activity (REA), originally isolated from human breast cancer cells, is present in mouse pituitary gonadotrope cell lines [9].
• 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 [6].
• Mutation of either Tyr248, Tyr357, or Tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type BAP/TFII-I in transfected COS-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation [6].
• Mature control astrocytes show a dramatic response to BAP by aggregating into a meshwork of rope-like structures that completely bridge over the peptide surface [10].

Associations of Phb2 with chemical compounds

• In luciferase reporter assays, REA decreased transcription, and this repression was sensitive to the deacetylase inhibitor trichostatin A [11].
• Our analysis also revealed that REA is an important repressor of ER transcriptional activity in the mammary gland under natural, as well as ovariectomized and estrogen-replaced, hormonal conditions [1].
• PGA-CDDP also increased the survival of mice bearing Bcap-37 cells with reference to PBS treatment or free CDDP treatment [12].

Physical interactions of Phb2

• Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation [13].

Other interactions of Phb2

• Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth [14].

Analytical, diagnostic and therapeutic context of Phb2

• Our findings suggest that the stimulation of pituitary ERalpha activity by low concentrations of TERP can occur by titration of corepressors such as REA [9].

References