Mice Lacking Pin1 Develop Normally, but Are Defective in Entering Cell Cycle from G0 Arrest

Fujimori, Fumihiro; Takahashi, K.; Uchida, Chiyoko; Uchida, Takafumi

doi:10.1006/bbrc.1999.1736

Cited by 206 publications

(204 citation statements)

References 9 publications

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“…Mice lacking Pin1 display immature germ cells, mammary gland impairment and retinal dystrophy when they get old . Furthermore, serum depletion induces G0 arrest in Pin1À/À MEF (Fujimori et al, 1999).…”

Section: Introductionmentioning

confidence: 94%

“…Pin1-deficient mice were generated according to our previous report (Fujimori et al, 1999). p53-null mice were first generated by Livingstone et al (1992), and were provided by DuPont Central & Research Development (Wilmington, DE, USA).…”

Section: Micementioning

confidence: 99%

“…To genotype the Pin1 locus, the primers WILD1.2A (5 0 -AAG GGA TTA GAA GCA AGA TTC G-3 0 ), 2L (5 0 -AGC ACC CGA TCC TGT TCT GCA A-3 0 ) and Start2 (5 0 -CAG AGG CCA CTT GTG TA-3 0 ) were used (Fujimori et al, 1999). To genotype the p53 locus, the primers x7 (5 0 -TAT ACT CAG AGC CGG CCT-3 0 ), x6.5 (5 0 -ACA GCG TGG TGG TAC CTT AT-3 0 ) and Neo19 (5 0 -CAT TCA GGA CAT AGC GTT GG-3 0 ) were used (Livingstone et al, 1992).…”

Section: Micementioning

confidence: 99%

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Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

et al. 2006

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Tumor suppressor p53 is essential for checkpoint control in response to a variety of genotoxic stresses. DNA damage leads to phosphorylation on the Ser/Thr-Pro motifs of p53, which facilitates interaction with Pin1, a pSer/pThr-Prospecific peptidyl prolyl isomerase. Pin1 is required for the timely activation of p53, resulting in apoptosis or cell cycle arrest. To investigate the physiological relationship between Pin1 and p53, we created Pin1À/Àp53À/À mice. These p53-deficient mice spontaneously developed lymphomas, mainly of thymic origin, as well as generalized lymphoma infiltration into other organs, including the liver, kidneys and lungs. Ablation of Pin1, in addition to p53, accelerated the thymic hyperplasia, but the thymocytes in these Pin1À/À p53À/À mice did not infiltrate other organs. The thymocytes in 12-week-old Pin1À/Àp53À/À mice were CD4 À CD8 À (double negative) and had significantly higher levels of the intracellular form of Notch1 (NIC) than the thymocytes of p53À/À or wild-type mice. Presenilin-1, a cleavage enzyme for NIC generation from full-length Notch1 was increased in the thymocytes of Pin1À/Àp53À/À mice. Pin1 depletion also inhibited the degradation of NIC by proteasomes. These results suggest that both Pin1 and p53 control the normal proliferation and differentiation of thymocytes by regulating the NIC level.

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Section: Introductionmentioning

confidence: 94%

Section: Micementioning

confidence: 99%

Section: Micementioning

confidence: 99%

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Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

et al. 2006

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“…Une des premières fonctions biologiques identifiées de Pin1 est son rôle dans la régulation du cycle cellulaire (transition G1/S, transition G2/M, mitose et cytodiérèse). Des fibroblastes de souris déficients pour Pin1 ne peuvent pas reprendre le cycle cellulaire lors d'une stimulation après un arrêt en G0 [8]. Ainsi, Pin1 contrôle la transition G0-G1/S en régulant, par exemple, l'expression et la localisation cellulaire de la cycline D1 [3,9] (Figure 2).…”

Section: La Prolifération Cellulaireunclassified

Pin1 : une peptidyl-prolylcis-transisomérase multifonctionnelle et une cible anticancéreuse prometteuse

Marsolier

Weitzman²

2014

Med Sci (Paris)

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> Les modifications post-traductionnelles sont essentielles pour contrôler finement les fonctions cellulaires des protéines. Un mécanisme peu connu, la peptidyl-prolyl cistrans isomérisation, joue également un rôle dans la régulation des protéines. Par exemple, la peptidyl-prolyl cis-trans isomérase Pin1 isomérise des motifs phosphorylés, induisant des changements structuraux de ses cibles et modulant ainsi leur stabilité, leur localisation, leur état de phosphorylation, leur activité et/ou leur interaction avec des partenaires. Pin1 est impliquée dans de nombreux processus cellulaires dont la prolifération et l'invasion cellulaires, ou encore l'induction et la maintenance de la pluripotence des cellules souches. De plus, Pin1 est surexprimée dans certains cancers humains. Ainsi, son inhibition constitue une piste thérapeutique prometteuse. < dans la structure de la protéine cible et régule ainsi ses fonctions. Les PPIases contrôlent donc de façon post-traductionnelle un grand nombre de protéines et sont impliquées dans de nombreux processus biologiques ou pathologiques humains (comme le cancer) [1]. Dans cette revue, nous nous intéresserons à Pin1 ainsi qu'à son rôle dans le développement des cellules tumorales. Structure et mécanismes d'action de Pin1Pin1 a été découverte lors d'un criblage double-hybride avec la protéine kinase mitotique NIMA (never in mitosis gene A) [2]. Chez la levure Saccharomyces cerevisiae, Pin1/Ess1 est la seule PPIase essentielle, ce qui démontre son importance biologique. Chez la levure, la délétion du gène est létale et induit un arrêt du cycle cellulaire [2]. Chez la souris, la délétion de Pin1 n'est pas létale, mais les souris mutantes présentent des phénotypes comparables à ceux des souris invalidées pour la cycline D1 [3]. Elles développent des anomalies de prolifération des tissus, comme une atrophie testiculaire, une dégéné-rescence de la rétine et un défaut de développement de l'épithélium mammaire lors de la gestation [3].

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“…Ess1 homologues have been studied in metazoans such as Drosophila melanogaster (Maleszka et al, 1996;Hsu et al, 2001), Xenopus (Winkler et al, 2000), mice and humans (Fujimori et al, 1999;Lu et al, 1996). In most of these organisms, Ess1/Pin1 is not essential for growth.…”

Section: Introductionmentioning

confidence: 99%

The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans

et al. 2005

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Cryptococcus neoformans is an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis. C. neoformans contains several genes encoding peptidyl-prolyl cis/trans isomerases (PPIases), enzymes that catalyse changes in the folding and conformation of target proteins. Three distinct classes of PPIases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. This paper reports the cloning and characterization of ESS1, which is believed to be the first (and probably only) parvulin-class PPIase in C. neoformans. It is shown that ESS1 from C. neoformans is structurally and functionally homologous to ESS1 from Saccharomyces cerevisiae, which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. In C. neoformans, ESS1 was found to be dispensable for growth, haploid fruiting and capsule formation. However, ESS1 was required for virulence in a murine model of cryptococcosis. Loss of virulence might have been due to the defects in melanin and urease production observed in ess1 mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential in C. neoformans suggests that, in this organism, some of its functions might be subsumed by other prolyl isomerases, in particular, cyclophilins Cpa1 or Cpa2. This is supported by the finding that ess1 mutants were hypersensitive to cyclosporin A. C. neoformans might therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.

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Mice Lacking Pin1 Develop Normally, but Are Defective in Entering Cell Cycle from G0 Arrest

Cited by 206 publications

References 9 publications

Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

Ablation of a peptidyl prolyl isomerase Pin1 from p53-null mice accelerated thymic hyperplasia by increasing the level of the intracellular form of Notch1

Pin1 : une peptidyl-prolylcis-transisomérase multifonctionnelle et une cible anticancéreuse prometteuse

The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans

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