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CIP/KIP and INK4 families as hostages of oncogenic signaling

Lucia Csergeová1, David Krbušek1, Radoslav Janoštiak2

  • 1BIOCEV-First Faculty of Medicine, Charles University, Prague, Czechia.

Cell Division
|April 2, 2024
PubMed

Insights

Cyclin-dependent kinase inhibitors (CKIs) from the CIP/KIP and INK4 families have dual roles in cancer. Understanding their complex functions is key to developing effective cancer treatments.

Area of Science:

  • Molecular Oncology
  • Cell Cycle Regulation
  • Cancer Biology

Background:

  • Cyclin-dependent kinase inhibitors (CKIs) are crucial regulators of the cell cycle.
  • CIP/KIP and INK4 families are well-known for their canonical tumor suppressor roles.
  • Emerging evidence reveals non-canonical functions, including tumor-promoting activities, influenced by posttranslational modifications and cellular context.

Purpose of the Study:

  • To review the canonical and non-canonical functions of CIP/KIP and INK4 CKIs.
  • To explore strategies for enhancing their tumor suppressor functions.
  • To discuss their potential in designing novel cancer therapies.

Main Methods:

  • Literature review of existing research on CIP/KIP and INK4 families.
  • Analysis of studies detailing CKI posttranslational modifications and subcellular localization.
  • Synthesis of information on CKI roles in various cancer contexts.

Main Results:

  • CKIs exhibit context-dependent functions, acting as both tumor suppressors and enhancers.
  • Posttranslational modifications, subcellular localization, and cell state significantly impact CKI activity.
  • Canonical functions involve inhibiting Cyclin-CDK complexes to regulate cell cycle progression.

Conclusions:

  • CKIs possess multifaceted roles in cancer, extending beyond their established tumor suppressor functions.
  • Targeting CKI modifications and localization could shift their activity towards tumor suppression.
  • Further understanding of CKI biology may lead to improved cancer treatment strategies.
Keywords:
CIP/KIPCancerCyclin-dependent kinase inhibitorsINK4Oncogenic signalingPosttranslational modificationTherapy

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