The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults

  title={The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults},
  author={Paola Zacchi and Monica Gostissa and Takafumi Uchida and Clio Salvagno and Fabio Avolio and Stefano Volinia and Ze’ev A. Ronai and Giovanni Blandino and Claudio Schneider and Giannino Del Sal},
The tumour suppressor p53 is important in the cell decision to either arrest cell cycle progression or induce apoptosis in response to a variety of stimuli. p53 post-translational modifications and association with other proteins have been implicated in the regulation of its stability and transcriptional activities. Here we report that, on DNA damage, p53 interacts with Pin1, a peptidyl-prolyl isomerase, which regulates the function of many proteins involved in cell cycle control and apoptosis… 
The prolyl-isomerase Pin1 activates the mitochondrial death program of p53
It is shown that upon stress-induced phosphorylation of p53 on Ser46 by homeodomain interacting protein kinase 2, Pin1 stimulates its mitochondrial trafficking signal, that is, monoubiquitination, and the strong requirement of Pin1 for the induction of mitochondrial apoptosis by this compound is demonstrated.
The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP
It is found that Pin1 is required for efficient loading of p53 on target promoters upon stress and is recruited to chromatin by p53 and stimulates binding of the p300 acetyltransferase and consequent p53 acetylation.
The Prolyl Isomerase Pin1 Affects Che-1 Stability in Response to Apoptotic DNA Damage*
Che-1 is down-regulated during the apoptotic process and the E3 ligase HMD2 physically and functionally interacts with Che-1 and promotes its degradation via the ubiquitin-dependent proteasomal system.
The Transcriptional Repressor hDaxx Potentiates p53-dependent Apoptosis*
It is demonstrated that the multifunctional protein hDaxx interacts with p53 and its homologues, both in vitro and in vivo, and modulates their transcriptional activity, and is identified as a possible integrating factor that coordinates the response of p53 family members.
Prolyl isomerase Pin1: a catalyst for oncogenesis and a potential therapeutic target in cancer
Pin1 regulates the expression of cyclin D1 by cooperating with Ras signaling and inhibiting the interaction ofβ -catenin with the tumor suppressor APC and also directly stabilizing cyclinD1 protein.
Che-1 modulates the decision between cell cycle arrest and apoptosis by its binding to p53
Analysis of genome-wide chromatin occupancy by p53 revealed that p53/Che1 interaction results in preferential transactivation of growth arrest p53 target genes over its pro-apoptotic target genes, suggesting Che-1 to be a promising yet attractive drug target for cancer therapy.
HOPS and p53: thick as thieves in life and death
HOPS/TMUB1 as p53 modifiers could be attractive candidates to elucidate apoptosis or other important transcriptional-independent functions which are key in cancer research in order to develop new therapeutic approaches.
Regulation of the p73 protein stability and degradation.


The cellular response to p53: the decision between life and death
The p53 tumor suppressor protein plays a crucial role in regulating cell growth following exposure to various stress stimuli. p53 induces either growth arrest, which prevents the replication of
Increased and altered DNA binding of human p53 by S and G2/M but not Gl cyclin-dependent kinases
It is reported here that p53 is efficiently and selectively phosphor-ylated by S and G2/M Cdks and also causes a distinctive conformational change in p53 as revealed by partial protease analysis, suggesting a potential regulatory mechanism of p53 activity.
Pin1 regulates turnover and subcellular localization of β-catenin by inhibiting its interaction with APC
It is shown that Pin1 regulates β-catenin turnover and subcellular localization by interfering with its interaction with adenomatous polyposis coli protein (APC) and its overexpression might contribute to the upregulation of β- catenin in tumours such as breast cancer.
Excess β‐catenin promotes accumulation of transcriptionally active p53
It is reported here that overexpression of β‐catenin results in accumulation of p53, apparently through interference with its proteolytic degradation, and is accompanied by augmented transcriptional activity of p 53 in the affected cells.
Mechanisms of p53-mediated apoptosis
There appears to be cell type variability in both the response to p53 expression and in the requirement for p53 transcriptional transactivation for the induction of apoptosis, and this may, in part, reflect the deregulated expression of E2F-1 in tumour cells.
p53 Death Star
A human peptidyl–prolyl isomerase essential for regulation of mitosis
Pinl is an essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity, and is structurally and functionally related to Essl/Ptfl, an essential protein in budding yeast.
Requirement of the prolyl isomerase Pin1 for the replication checkpoint.
Premature mitotic entry in the absence of Pin1 was accompanied by hyperphosphorylation of Cdc25, activation of CDC2/cyclin B, and generation of epitopes recognized by the mitotic phosphoprotein antibody, MPM-2, therefore, Pin1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.
Jun NH2-Terminal Kinase Phosphorylation of p53 on Thr-81 Is Important for p53 Stabilization and Transcriptional Activities in Response to Stress
The studies identify an additional mechanism for the regulation of p53 stability and functional activities in response to stress that tightly regulates its stability and transcriptional activities.