Disease relevance of Pip

• In human breast cancer cells, the expression of PIP/gross cystic disease fluid protein-15 is stimulated by androgen and PRL, and inhibited by estrogen [1].
• Here we describe repressible (PipOFF) as well as inducible (PipON) systems for regulated gene expression in mammalian cells, based on the repressor Pip (pristinamycin-induced protein), which is encoded by the streptogramin resistance operon of Streptomyces coelicolor [2].
• A Pip dominant negative mutant that cannot synergize with E47 inhibited enhancer activity in plasmacytoma cells and could not activate transcription in pre-B cells [3].
• AIM: To study the effects of piperine (Pip) on several experimental gastric ulcers in rats and mice [4].
• Gross Cystic Disease Fluid Protein (GCDFP-15) is a 60,000 dalton glycoprotein isolated from human breast cyst fluid, composed of four 15,000 dalton monomers [5].

High impact information on Pip

• 1. Thus, during B-cell activation and differentiation, Pip may function both as an activator to promote B cell-specific gene expression and as a repressor to inhibit the antiproliferative effects of alpha/beta-interferons [6].
• When stably expressed, the wild-type fused dimer strongly repressed the expression of a rearranged immunoglobulin lambda gene, thereby establishing the functional importance of PU.1-Pip complexes in B cell gene expression [7].
• In addition, these effects do not reflect a specific insulin requirement for prolactin sensitivity; epidermal growth factor can support prolactin-induced total RNA synthesis as well as insulin can [8].
• Using electrophoretic mobility shift assays, we found that Pip can bind to the heavy-chain intron enhancer region [3].
• However, a Pip dominant negative mutant inhibited germ line I micro transcripts [3].

Biological context of Pip

• In the rat submaxillary gland, PIP/SMGP gene expression was confined to the acinar cells [1].
• Regulation of the PIP/SMGP gene in vivo may provide a useful model system to study the mechanism of down-regulation of expression by androgen in a tissue-specific manner [1].
• Nearing the end of gestation, E18, mSMGP/mPIP transcripts were localized in the proacinar cells of the gland, and gene expression continued to be maintained following birth [9].
• We also identified a Pip domain (residues 207 to 300) that appears to mask Pip transactivation potential [10].
• Through a series of mutagenesis experiments, we identified the Pip sequences necessary for transcriptional activation and for synergy with E47 [10].

Anatomical context of Pip

• PIP/SMGP messenger RNA expression was only detected in the lacrimal and submaxillary glands of the rodents [1].
• PRL had no effect on the regulation of PIP/SMGP in either salivary or lacrimal glands [1].
• In addition, during early postnatal development, mSMGP/mPIP gene expression was detected in the other two major salivary glands, the sublingual and parotid, as well as in the lacrimal gland and in reproductive tissues [9].
• In addition, we found that in fibroblasts Pip greatly increased E47 induction of germ line I micro transcripts associated with somatic rearrangement and isotype class switching [3].
• The inhibitory rates were 16.9%, 36.0%, and 48.3% in stress ulcers; 4.4%, 51.1%, and 64.4% in indometacin ulcers; 19.2%, 41.5%, and 59.6% in HCl ulcers; 4.8%, 11.9%, and 26.2% in pyloric ligation ulcers, respectively; Pip inhibited the volume of gastric juice, gastric acidity, and pepsin A activity [4].

Associations of Pip with chemical compounds

• Second, a conformational change in the PU.1 PEST domain, apparently mediated by serine phosphorylation, induces a conformational change in Pip enabling it to bind to DNA [11].
• Ceftriaxone and ticarcillin-clavulanate treatment groups developed persistently high levels of stool VRE compared with both the saline and the piperacillin-tazobactam (Pip-Taz) groups (P<.008) [12].
• In hypophysectomized ovariectomized animals, the administration of estradiol restored the Hageman factor titer to normal levels, whereas the infusion of prolactin induced a dramatic rise in the Hageman factor titer to the degree observed in nonhypophysectomized estrogen-treated rats [13].
• In HC11 cells, NF-kappaB p50/p65 activity was inversely correlated with prolactin-induced STAT5 tyrosine phosphorylation, expression of endogenous beta-casein gene, and of a transfected beta-casein gene promoter reporter construct [14].
• Unlike explants from normal virgin mouse mammary gland, exposure to insulin, hydrocortisone, and prolactin induced an increase in casein synthesis in HAN explant cultures which was independent of DNA synthesis [15].

Regulatory relationships of Pip

• Specifically, we show that caveolin-1 expression blocks prolactin-induced activation of a STAT5a-responsive luciferase reporter in mammary epithelial cells [16].
• The MEK inhibitor PD 098059 inhibits prolactin-induced Nb2 cell mitogenesis but not milk product synthesis in cultured mouse mammary tissues [17].
• Nitric oxide (NO) enhances prolactin-stimulated DNA synthesis and inhibits prolactin-induced differentiation in mouse mammary epithelium [18].

Other interactions of Pip

• The receptor activator of NF-kappaB ligand induces the expression of tartrate-resistant acid phosphatase (TRAP) and transcription factor, PU.1-interacting protein (Pip), during osteoclastogenesis [19].
• Stat5 was initially identified as a prolactin-induced member of the signal transducer and activator of transcription (Stat) family in sheep [20].
• Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of mammary epithelial cells [21].
• Retinoyl beta-glucuronide (RAG) and retinyl beta-glucuronide (ROG) inhibit prolactin-induced morphological developments in cultured mouse mammary gland, and are equally effective in depressing prolactin and steroid hormone-induced DNA synthesis in the same tissue [22].
• W-13 (N-(4-aminobutyl)-5-chloro-2-naphthalenesulphonamide), a calmodulin inhibitor, reduced prolactin-induced differentiation by 80% while inhibiting insulin- and cortisol-induced RNA synthesis only 40% [23].

Analytical, diagnostic and therapeutic context of Pip

• In the present study we employed reverse transcriptase-polymerase chain reaction followed by rapid amplification of complementary DNA (cDNA) ends to amplify the PIP cDNA homolog, the submaxillary gland protein (SMGP) in the mouse [1].
• Using the mouse PIP/SMGP cDNA as a probe, we examined the tissue- and cell-specific expression of PIP/SMGP messenger RNA by in situ hybridization and Northern blot analysis of mouse and rat tissues [1].
• In the male rat lacrimal gland, castration resulted in an increase in expression, and in both male and female rats, androgen replacement abolished PIP/SMGP gene expression [1].
• Mouse mammary gland organ culture technique was utilized to determine the effects of retinoids on the prolactin-induced structural differentiation of the mammary gland [24].
• The development of acute tolerance to prolactin-induced analgesia in mice was identified by using the writhing test [25].

References