2010 年 30 巻 6 号 p. 507-519
Stable cell-cycle arrest is known as “cellular senescence” and is triggered by various stresses. Senescent cells show a series of alterations, including a flat and enlarged morphology, increased in non-specific acidic β-galactosidase activity, chromatin condensation, and changes in gene expression patterns. The onset and maintenance of senescence are regulated by two tumor suppressor proteins, p53 and Rb. The expression of p53 and Rb is regulated by two distinct proteins, Arf and p16Ink4a, respectively, which are encoded by cdkn2a. Jun dimerization protein (JDP2) is a histone chaperone, which has activities in the inhibition of histone acetyltransferase and in nucleosome assembly/disassembly. Therefore, JDP2 plays key roles in cell growth, cell differentiation, and senescence by regulating the expression of genes. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC-1 and PRC-2) to the promoter of the gene encoding p16Ink4a and inhibits the methylation of lysine 27 of histone H3 (H3K27). In fact, the PRCs associate with the p16Ink4a/Arf locus in young proliferating cells and dissociate from it in aged senescent cells. Therefore, it seems that chromatinremodeling factors that regulate the association and dissociation of PRC and are controlled by JDP2 might be important players in the senescence program. The molecular mechanisms that underline the action of JDP2 in cellular aging and replicative senescence by mediating the dissociation of PRCs from the p16Ink4a/Arf locus are discussed.