CBX8
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Chromobox protein homolog 8 (Polycomb 3 homolog) (Pc3) (hPc3) (Rectachrome 1) [PC3] [RC1]
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Chromobox protein homolog 8 (Polycomb 3 homolog) (Pc3) (hPc3) (Rectachrome 1) [PC3] [RC1]
The proto-oncogene PIM1 encodes Ser/Thr kinase and regulates cell growth, differentiation and apoptosis. However, more and more studies including ours have found that PIM1 can induce senescence in normal human diploid fibroblasts and behave as a tumor suppressor. But the relevant molecular mechanism of this process is not yet clear. It has been reported that Chromobox homolog 8 (CBX8) binds directly to INK4A as a transcriptional repressor, thereby suppressing stress-induced senescence. Here we report that PIM1 can phosphorylate CBX8 to promote its degradation, thereby up-regulating p16, during PIM1-induced cell senescence. Overexpression of CBX8 can inhibit PIM1-induced cell senescence. These data suggest that to promote CBX8 degradation may be an important molecular mechanism of PIM1-induced cell senescence.
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Although tyrosine kinase inhibitor (TKI) therapies are highly effective in the treatment of chronic myeloid leukemia (CML), frequent recurrence limits their usage and demands new approaches for CML therapy. Stress-induced premature senescence (SIPS) is considered a potential anticancer treatment, but the underlying mechanism remains elusive. Here, we report that Sirtinol, a known SIRT1 inhibitor, induces premature senescence and growth arrest in K562 CML cells. Chromobox homolog 8 (CBX8) suppresses the Sirtinol-induced premature senescence, which is reversed by CBX8 knockdown. Upon Sirtinol treatment, the phosphorylation of AKT1, p27KIP1 and RB is severely downregulated. However, CBX8 overexpression enhances phosphorylation and, thereby, promotes the transcriptional activity of E2F1, both of which are impaired upon CBX depletion. These data suggest that CBX8 modulates SIPS through the RB-E2F1 pathway in CML cells and provide important insight into its application in CML treatment.
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