page_title: INK4
section_title: Function
hierarchical_section_title: INK4 / Function
caption_attribution_description: English: Multiple myeloma paper
context_page_description: INK4 is a family of cyclin-dependent kinase inhibitors. The members of this family are inhibitors of CDK4, and of CDK6. The other family of CKIs, CIP/KIP proteins are capable of inhibiting all CDKs. Enforced expression of INK4 proteins can lead to G1 arrest by promoting redistribution of Cip/Kip proteins and blocking cyclin E-CDK2 activity. In cycling cells, there is a resassortment of Cip/Kip proteins between CDK4/5 and CDK2 as cells progress through G1. Their function, inhibiting CDK4/6, is to block progression of the cell cycle beyond the G₁ restriction point. In addition, INK4 proteins play roles in cellular senescence, apoptosis and DNA repair.
  INK4 proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis.
  INK4 proteins are highly similar in terms of structure and function, with up to 85% amino acid similarity. They contain multiple ankyrin repeats.
context_section_description: INK4 proteins are cell-cycle inhibitors.  When they bind to CDK4 and CDK6, they induce an allosteric change that leads to the formation of CDK-INK4 complexes rather than CDK-cyclin complexes.  This leads to an inhibition of retinoblastoma (Rb) phosphorylation downstream.  Therefore, the expression of p15INK4b or p16INK4A keeps the Rb-family proteins hypophosphorylated.  This allows the hypophosphorylated Rb to repress transcription of S-phase genes causing cell cycle arrest in the G1 phase.
caption: INK4 in cyclin/CDK pathway[1]
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