Cell cycle must be carefully controlled to ensure genetic materials are replicated once and only once per cycle and equal sister chromatid segregation into two daughter cells. While cyclin-dependent kinases are master regulators of cell cycle, p53 and NF-κB pathways are also critical for the regulation of the cell cycle and especially the targets modulated by Par-4. Par-4 can be both cytosolic and nuclear. Cytosolic Par-4 inhibits nuclear localization of NF-κB and decreases Bcl-2 expression, leading to G1 arrest. Mechanistically, Par-4 can directly interact with NF-κB or represses ζPKC activity thus inhibits NF-κB indirectly, eventually resulting in inhibition of DROSHA expression and regulation of miRNA. Nuclear Par-4 functions as co-transcriptional factor of THAP for CCAR1, which subsequently activates the p53/p21 axis, resulting in G1 arrest. While Par-4-associated inhibition of DNA topoisomerase activity results in S phase arrest, the distribution of Par-4 in mitotic cells determines the fate of daughter cells. PLK1 is a serine/threonine kinase involved in many cell cycle-related events, including Cdk1 activation, centrosome maturation, microtubule-kinetochore attachment, bipolar spindle formation, sister chromatid segregation, and cytokinesis. PLK1 also has well-established roles in DNA damage response, especially p53 regulation, via direct phosphorylation of multiple p53 regulators such as Topors, GTSE1, and Numb. Further, PLK1 is transcriptionally regulated by NF-κB. Based on all the research performed so far, we are proposing an intriguing working model in which NF-κB, PLK1, and Par-4 are well integrated in the context of acquisition of radioresistance of prostate cancer.

Original languageEnglish
Title of host publicationTumor Suppressor Par-4
Subtitle of host publicationStructural Features, Molecular Mechanisms and Function
Number of pages33
ISBN (Electronic)9783030735722
StatePublished - Jan 1 2022

Bibliographical note

Publisher Copyright:
© Springer Nature Switzerland AG 2022.


  • Bcl-2
  • CCAR1
  • Cell cycle
  • NF-κB
  • PLK1
  • Par-4
  • THAP1
  • p21
  • p53

ASJC Scopus subject areas

  • Medicine (all)


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