Disease relevance of Pttg1

• Securin was also independently identified as PTTG (pituitary tumor transforming gene), a gene overexpressed in pituitary tumors [9] [1].
• Here we show that mice lacking PTTG (PTTG -/-) are, surprisingly, viable and fertile; but they have testicular and splenic hypoplasia, thymic hyperplasia, and thrombocytopenia [2].
• We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse [3].
• Suppression of lung cancer with siRNA targeting PTTG [4].
• We tested whether mPTTG exhibits securin properties in mouse insulin-secreting insulinoma MIN6 cells, using a live-cell system to monitor mitosis in cells transfected with an enhanced green fluorescent protein (EGFP)-tagged mPTTG conjugate (mPTTG-EGFP) [5].

High impact information on Pttg1

• Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes [6].
• Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1 [7].
• We have created conditional knockout alleles of the mouse Separase and Securin genes [8].
• Separase is a protease whose liberation from its inhibitory chaperone Securin triggers sister chromatid disjunction at anaphase onset in yeast by cleaving cohesin's kleisin subunit [8].
• Mice or cell lines deficient in PTTG expression, however, are surprisingly viable [9].

Chemical compound and disease context of Pttg1

• CONCLUSION: We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level [10].
• Mice with Pttg inactivation exhibit pituitary hypoplasia, whereas targeted pituitary PTTG overexpression driven by alpha-subunit glycoprotein (alphaGSU) promoter results in focal pituitary hyperplasia [11].

Biological context of Pttg1

• In budding yeast, loss of securin results in precocious sister chromatid separation when the microtubule spindle is disrupted [12].
• After securin degradation, Separase cleaves the cohesins and triggers chromatid separation, a prerequisite for anaphase [13].
• The nuclear transport factors Rae1 and Nup98, which convert into mitotic checkpoint proteins in M-phase, further prevent chromosome missegregation by assembling into a complex with APC(Cdh1) and delaying APC(Cdh1)-mediated ubiquitination of securin [14].
• Shortly after germinal vesicle breakdown, immunoreactive securin accumulated around the condensed chromosomes at prometaphase I [15].
• Securin was increased again at metaphase II, while it was decreased at anaphase II [15].

Anatomical context of Pttg1

• We generated a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells [12].
• In germinal vesicle-stage oocytes, immunostaining of securin was mainly localized in the germinal vesicle [15].
• The results indicated that securin is indispensable for normal pancreatic beta cell proliferation [9].
• BrdUrd incorporation of islet cells in PTTG-null mice was approximately 65% lower (P < 0.005) than in the WT pancreas, whereas apoptosis rates were similar [9].
• PTTG -/- mouse embryo fibroblasts exhibited aberrant cell cycle progression with prolonged G2-M phase and binucleated and multinucleated nuclei with increased aneuploidy [2].

Associations of Pttg1 with chemical compounds

• Here we show that PTTG disruption in mice (PTTG-/-) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alphabeta cell ratio [9].
• Here we show that stabilisation of cyclin B in nocodazole can be sustained for several hours and is associated with stabilisation of securin [16].
• Because Ca(2+) spiking was not inhibited by Delta 90 cyclin B1, the degradation timing of securin, visualized by coupling it to EGFP, was unaffected [17].
• The release of HeLa cells from metaphase arrest in the presence of exogenous H(2)O(2) inhibited the ubiquitination of cyclin B1 as well as the degradation of cyclin B1 and securin that were apparent in the absence of H(2)O(2) [18].
• Concomitantly, arsenite markedly diminished the securin protein expression and induced the abnormal sister chromatid separation [19].

Physical interactions of Pttg1

• Here we show that Rae1 and Nup98 not only form a complex with APC(Cdh1) in prometaphase but also with securin [20].

Regulatory relationships of Pttg1

• Cyclin B1 degradation reduces maturation (M-phase)-promoting factor (MPF) activity and securin degradation allows sister chromatid separation [17].
• Depletion of securin increases arsenite-induced chromosome instability and apoptosis via a p53-independent pathway [19].

Other interactions of Pttg1

• Although securin/separase/cohesion pathway was reported to regulate chromosome segregation during meiotic metaphase-to-anaphase transition, little biochemical evidence was provided [15].
• Most of the cells expressing the PTTG gene were found in the lower part of the ventricular zone suggesting that the level of PTTG mRNA is regulated during different phases of the mitotic cycle [21].
• Besides, arsenite decreased the levels of securin proteins to a similar degree in both the p53-functional and -mutational cells [19].

Analytical, diagnostic and therapeutic context of Pttg1

• In both mouse and pig oocytes, Western blot analysis showed that securin protein was low at germinal vesicle stage, reached the highest level at metaphase I, while decreased at anaphase I [15].
• Microinjection of securin antibody into MII-arrested oocytes leads to the degradation of Rec8 [15].
• We present the first time/space analysis using in situ hybridization for PTTG and prc1 genes during development of the mouse telencephalon [21].
• Microarray analysis of the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1) [3].
• Confocal microscopy showed that PTTG-overexpressing cells have enlarged nuclei and marked redistribution of chromatin, and electron microscopy of alphaGSU.PTTG pituitaries showed enlarged gonadotrophs with prominent Golgi complexes and numerous secretory granules [11].

References