Pituitary Tumor Transforming Gene (PTTG) Regulates Placental JEG-3 Cell Division and Survival: Evidence from Live Cell Imaging

Yu, Run; Ren, Shaolei; Horwitz, Gregory A.; Wang, Zhiyong; Melmed, Shlomo

doi:10.1210/mend.14.8.0501

Cited by 82 publications

(82 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Plasmids-ICER-II␥ (pSVICER-II␥), ICER-II␥(Ala-41) (pSVICER-II␥(Ala-41)), and CREM (pSVCREM) cDNAs used for transient transfection are under the SV40 promoter (12,15,30). pFLAGCMV2-hCDC34 (29) was used for transient transfections for the expression of the ubiquitin-conjugating enzyme Cdc34.…”

Section: Methodsmentioning

confidence: 99%

Mitogen-activated Protein Kinase Phosphorylates and Targets Inducible cAMP Early Repressor to Ubiquitin-mediated Destruction

Yehia¹,

Schlotter²,

Razavi³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Inducible cAMP early repressor (ICER) is an important mediator of cAMP antiproliferative activity that acts as a putative tumor suppressor gene product. In this study, we examined the regulation of ICER protein by phosphorylation and ubiquitination in human choriocarcinoma JEG-3 and mouse pituitary AtT20 cells. We found that cAMP stabilized ICER protein by inhibiting the mitogen-activated protein kinase (MAPK) cascade. Activation of the MAPK pathway increased ICER phosphorylation. ICER phosphorylation was abrogated by inhibition of the MAPK pathway either by cAMP or directly by the MAPK inhibitor PD098059. The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4 -5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway. These results present a novel cell signaling crosstalk mechanism at the cell nucleus between the MAPK and cAMP pathways, whereby MAPK targets a repressor of the cAMP-dependent gene expression for ubiquitination and proteasomal degradation.The MAPK 1 pathway controls cell growth by regulating gene expression, protein synthesis, nucleotide synthesis, the interaction between cyclins and cyclin-dependent kinases, and protein stability by ubiquitin-mediated proteasomal degradation (Refs. 1 and 2 and references therein). In the classic pathway, activation of MAPK occurs by peptide growth factors that bind to a transmembrane tyrosine kinase receptor. This results in the activation of the small GTP-binding protein Ras that recruits a member of the Raf kinase family (Raf-1, A-Raf, or B-Raf) to the plasma membrane. Raf phosphorylates and activates the MEKs (MEK1 and MEK2), which in turn activates the MAPKs ERK1 and ERK2 by phosphorylation on threonine and tyrosine.

show abstract

Section: Methodsmentioning

confidence: 99%

Mitogen-activated Protein Kinase Phosphorylates and Targets Inducible cAMP Early Repressor to Ubiquitin-mediated Destruction

Yehia¹,

Schlotter²,

Razavi³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…8C, middle panel). The former four genes are known to exhibit peak mRNA levels at the G 1 /S boundary of the cell cycle (45,46), and the latter two genes exhibit peak mRNA levels at G 2 and M phases (47,48). Taken together, it appeared as if the cells started to progress from G 0 or G 1 phase after the glucose addition.…”

Section: Glucose As a Direct Resetting Signal For Peripheral Clocks-mentioning

confidence: 98%

Glucose Down-regulates Per1 and Per2mRNA Levels and Induces Circadian Gene Expression in Cultured Rat-1 Fibroblasts

Hirota

Okano

Kokame

et al. 2002

Journal of Biological Chemistry

288

204

View full text Add to dashboard Cite

In mammals, peripheral circadian clocks are present in most tissues, but little is known about how these clocks are synchronized with the ambient 24-h cycles. By using rat-1 fibroblasts, a model cell system of the peripheral clock, we found that an exchange of the culture medium triggered circadian gene expression that was preceded by slow down-regulation of Per1 and Per2 mRNA levels. This profile contrasts to the immediate up-regulation of these genes often observed for clock resetting. The screening of factor(s) responsible for the down-regulation revealed glucose as a key component triggering the circadian rhythm. The requirement of both glucose metabolism and RNA/protein synthesis for the down-regulation suggests the involvement of gene(s) immediately up-regulated by glucose metabolism. An analysis with high density oligonucleotide microarrays identified >100 glucose-regulated genes. We found among others immediately up-regulated genes encoding transcriptional regulators TIEG1, VDUP1, and HES1, in addition to cooperatively regulated genes that are associated with cholesterol biosynthesis and cell cycle. The immediate up-regulation of Tieg1 and Vdup1 expression was dependent on glucose metabolism but not on protein synthesis, suggesting that the transcriptional regulators mediate the glucose-induced down-regulation of Per1 and Per2 expression. These results illustrate a novel mode of peripheral clock resetting by external glucose, a major food metabolite.

show abstract

“…Zhang et al (35) ------p-= 5=-3 c-myc ~ ~ (26). Data from our laboratory and others have since shown that PTTG overexpression results in cell cycle arrest and apoptosis (40,66,74), and these effects are mediated through bothp53 dependent and independent pathways.…”

Section: Tumorigenesismentioning

confidence: 96%

“…PTTG functions as human securin to ensure that there is no premature separation of sister chromatids by inhibiting separase, which is liberated from securin to degrade cohesin bound to sister chromatids at anaphase ( Figure 5) The level of PTTG expression is increased rapidly in proliferating cells and is regulated in a cell cycle-dependent manner (47,66). PTTG mRNA and protein-levels are low at the GIIS inter-phase, and gradually increases during S phase with maximum expression at M phase.…”

Section: Functionsmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of angiogenic factors by pituitary tumor transforming gene (PTTG) in tumorigenesis.

Malik¹

View full text Add to dashboard Cite

Pituitary Tumor Transforming Gene (PTTG) Regulates Placental JEG-3 Cell Division and Survival: Evidence from Live Cell Imaging

Cited by 82 publications

References 23 publications

Mitogen-activated Protein Kinase Phosphorylates and Targets Inducible cAMP Early Repressor to Ubiquitin-mediated Destruction

Mitogen-activated Protein Kinase Phosphorylates and Targets Inducible cAMP Early Repressor to Ubiquitin-mediated Destruction

Glucose Down-regulates Per1 and Per2mRNA Levels and Induces Circadian Gene Expression in Cultured Rat-1 Fibroblasts

Regulation of angiogenic factors by pituitary tumor transforming gene (PTTG) in tumorigenesis.

Contact Info

Product

Resources

About