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PIN1 in Cell Cycle Control and Cancer

Chi-Wai Cheng1, Eric Tse1

  • 1Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

Frontiers in Pharmacology
|December 12, 2018
PubMed

Insights

The peptidyl-prolyl cis/trans isomerase PIN1 regulates cell cycle proteins through phosphorylation-dependent prolyl isomerization. PIN1 inhibition shows therapeutic potential in cancer treatment.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Cell cycle progression is regulated by cyclin-dependent kinases (CDKs) and protein phosphorylation.
  • PIN1, a peptidyl-prolyl cis/trans isomerase, acts as a key post-phosphorylation regulator of CDK-phosphorylated proteins.
  • PIN1 specifically targets phosphorylated serine or threonine residues preceding proline (pSer/Thr-Pro) motifs.

Purpose of the Study:

  • To review the essential roles of PIN1 in cell cycle regulation.
  • To explore the mechanisms of PIN1 overexpression in cancers.
  • To summarize the therapeutic potential of PIN1 inhibitors in cancer therapy.

Main Methods:

  • Literature review of studies on PIN1 function and regulation.
  • Analysis of PIN1's role in modulating cell cycle proteins like Rb, cyclin D1, cyclin E, p27, Cdc25C, and Wee1.
  • Examination of cancer-associated mechanisms of PIN1 overexpression.

Main Results:

  • PIN1 fine-tunes cell cycle protein functions via phosphorylation-dependent prolyl isomerization.
  • Dysregulation and overexpression of PIN1 are implicated in various cancers.
  • PIN1 inhibitors demonstrate significant therapeutic potential in preclinical cancer models.

Conclusions:

  • PIN1 is a critical regulator of cell cycle progression by modifying key regulatory proteins.
  • Targeting PIN1 offers a promising strategy for novel cancer therapies.
  • Further research into PIN1's role in tumorigenesis could unveil new therapeutic avenues.
Keywords:
PIN1cell cyclecheckpointisomerizationphosphorylation

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