DescriptionThe INK4a locus on chromosome 9p21 is frequently affected in human tumors. It encodes two structurally distinct tumor suppressor proteins, p16INK4a and the alternative reading frame protein, ARF (p14ARF in human and P19ARF in mouse). These two proteins interact with the upstream proteins: retinoblastoma protein and p53 tumor suppressors, respectively. Each of these proteins has a role in the senescence of primary cells, activates pathways for cell cycle control and tumor suppression. The p14ARF (or P19ARF in mouse) proteins can induce both G1 and G2 phase arrest in a manner that depends on functional p53. The mouse and human ARF proteins have different functions in tumor suppression; this distinction may contribute to the different levels of tumor proneness of these species.
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