Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships

Mantovani, Fiamma; Zannini, Alessandro; Rustighi, Alessandra; Sal, Giannino Del

doi:10.1016/j.bbagen.2015.01.013

Cited by 25 publications

(33 citation statements)

References 197 publications

(267 reference statements)

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“…However, it remains controversial whether PIN1 acts as a tumor promoter (10,14,(18)(19)(20) or tumor suppressor (11,12,22). TP53 is one of the more than 50 critical regulatory proteins catalyzed by PIN1 (8,13). TP53 mutation is also one of the most common genetic alterations in HCC and leads to the accumulation of mutant TP53 protein that endows oncogenic activities (5,7,23).…”

Section: Discussionmentioning

confidence: 99%

“…These contradictory reports regarding the function of PIN1 in oncogenesis suggest that PIN1 can either function as a conditional tumor promoter or suppressor. Among the many documented targets of PIN1-mediated prolyl-isomerization that regulate cell fate, TP53 represents the most relevant one and is frequently deregulated in cancer (8,10,13). A recent study has shown that PIN1 conveys oncogenic signals in concert with mutant TP53 protein to promote aggressiveness in breast cancer cells, and concomitant high PIN1 expression and TP53 mutation have been proposed as an independent prognostic factor of poor clinical outcome in breast cancer patients (14).…”

Section: Introductionmentioning

confidence: 99%

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PIN1 in hepatocellular carcinoma is associated with TP53 gene status

et al. 2016

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Phosphorylation of proteins on serine/threonine residues that precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase PIN1. PIN1-mediated prolyl-isomerization induces cell cycle arrest and growth inhibition through the regulation of target proteins, including TP53. We examined whether PIN1 acts in a different manner according to TP53 gene status in hepatocellular carcinoma (HCC). We investigated the expression of PIN1 and TP53 proteins in 119 HCC tissue samples. We also analyzed PIN1 expression in combination with TP53 gene mutation and its correlation with the clinical outcome. In addition, we used synthetic small interfering RNA to silence PIN1 gene expression in TP53 wild-type and TP53 mutant HCC cell lines, and then evaluated cell proliferation, migration and invasion. Expression of PIN1 was strongly associated with expression of TP53 protein or TP53 mutation of HCC samples. PIN1 and TP53 expression in TP53 mutant HCC cell lines was higher than that in TP53 wild-type HCC cell lines. Silencing of PIN1 in HLE cells containing mutant TP53 significantly decreased cell proliferation, migration and invasion. In contrast to PIN1 silencing in HLE cells, PIN1 silencing in HepG2 cells containing functional wild-type TP53 resulted in enhanced tumor cell proliferation. HCC patients bearing PIN1 expression with wild-type TP53 were predicted to demonstrate favorable relapse-free survival. Our results suggest that PIN1 plays a role in cancer cell proliferation, migration and invasion in a different manner according to the TP53 gene mutation status in HCC. In particular, interaction of PIN1 with mutant TP53 can act as a tumor promoter and increase its oncogenic activities in HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PIN1 in hepatocellular carcinoma is associated with TP53 gene status

et al. 2016

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“…It appears that Pin1 represents a common mediator linking proapoptotic cooperative activity of the p53 family members. As a regulator of p53, Pin1 regulates many cellular responses related to cell cycle and cell death, including genotoxic response, apoptosis, and mitochondrial apoptotic function (Wulf et al, 2002;Zacchi et al, 2002;Zheng et al, 2002;Follis et al, 2015;Mantovani et al, 2015).…”

Section: Stability Of Transcription Factorsmentioning

confidence: 99%

Pinning Down the Transcription: A Role for Peptidyl-Prolyl cis-trans Isomerase Pin1 in Gene Expression

Chen

2020

Front. Cell Dev. Biol.

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Pin1 is a peptidyl-prolyl cis-trans isomerase that specifically binds to a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) motif and catalyzes the cis-trans isomerization of proline imidic peptide bond, resulting in conformational change of its substrates. Pin1 regulates many biological processes and is also involved in the development of human diseases, like cancer and neurological diseases. Many Pin1 substrates are transcription factors and transcription regulators, including RNA polymerase II (RNAPII) and factors associated with transcription initiation, elongation, termination and post-transcription mRNA decay. By changing the stability, subcellular localization, protein-protein or protein-DNA/RNA interactions of these transcription related proteins, Pin1 modulates the transcription of many genes related to cell proliferation, differentiation, apoptosis and immune response. Here, we will discuss how Pin regulates the properties of these transcription relevant factors for effective gene expression and how Pin1-mediated transcription contributes to the diverse pathophysiological functions of Pin1.

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“…Adoptive gene transfer experiments in the mouse hematopoietic system directly demonstrated that mutations at codon 58 (one of the hotspots in BL) augment the oncogenic potential of c- myc [10]. On this basis, one might hypothesize that, like Thr 58 mutation, a decrease in Pin1 activity should potentiate the oncogenic action of Myc: this putative tumor suppressive effect of Pin1 might be further reinforced by its positive action on p53 [11, 15], a key suppressor of Myc-induced lymphomagenesis [16]. …”

Section: Introductionmentioning

confidence: 99%

Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc

et al. 2016

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The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma and substitutions in codon 58 stabilize the Myc protein or augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 and Thr 58 provides a landing pad for the peptidyl prolyl-isomerase Pin1, which in turn promotes Ser 62 dephosphorylation and Myc degradation. However, the role of Pin1 in Myc-induced lymphomagenesis remains unknown. We show here that genetic ablation of Pin1 reduces lymphomagenesis in Eμ-myc transgenic mice. In both Pin1-deficient B-cells and MEFs, the proliferative response to oncogenic Myc was selectively impaired, with no alterations in Myc-induced apoptosis or mitogen-induced cell cycle entry. This proliferative defect wasn't attributable to alterations in either Ser 62 phosphorylation or Myc-regulated transcription, but instead relied on the activity of the ARF-p53 pathway. Pin1 silencing in lymphomas retarded disease progression in mice, making Pin1 an attractive therapeutic target in Myc-driven tumors.

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Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships

Cited by 25 publications

References 197 publications

PIN1 in hepatocellular carcinoma is associated with TP53 gene status

PIN1 in hepatocellular carcinoma is associated with TP53 gene status

Pinning Down the Transcription: A Role for Peptidyl-Prolyl cis-trans Isomerase Pin1 in Gene Expression

Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc

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