Components of the evolutionarily conserved complex of HIRA, ...

created [InstanceEdit:4648283] Orlic-Milacic, M, 2013-09-30
dbId 4648286
displayName Components of the evolutionarily conserved complex of HIRA, ...
modified [InstanceEdit:4650046] Orlic-Milacic, M, 2013-10-01
schemaClass Summation
text Components of the evolutionarily conserved complex of HIRA, ASF1A, UBN1 and CABIN1 accumulate in PML bodies of pre-senescent cells, and relocate to SAHF (senescence-associated heterochromatic foci) in senescent cells, with SAHF relocation depending on the functional RB1 and TP53 pathways (Zhang et al. 2005, Ye et al. 2007, Zhang et al. 2007). The reorganization of heterochromatin into SAHFs is accompanied by reduction in the amount of total and chromatin-bound lamin B1 (LMNB1), and high levels of LMNB1 interfere with SAHF formation (Sadaie et al. 2013). High-mobility group A proteins, HMGA1 and HMGA2, are enriched on chromatin of senescent cells, predominantly localizing to SAHFs, and high HMGA1 and HMGA2 levels, in cooperation with p16-INK4A, promote SAHF formation and repression of E2F target genes in senescent cells. Overexpression of CDK4 and MDM2, which are frequently co-amplified with HMGA2 in cancer cells as a part of 12q13-15 chromosomal band amplification, bypasses HMGA2 and HMGA1 induced cell cycle arrest and SAHF formation (Narita et al. 2006). The accumulation of HMGA proteins on senescent cell chromatin and SAHF formation is accompanied by the loss of the linker histone H1, probably due to a posttranslational mechanism (Funayama et al. 2006). A chromatin remodeling protein EP400 (p400), which is able to bind CDKN1A (p21) promoter and inhibit TP53-mediated activation of CDKN1A transcription, negatively regulates SAHF formation (Chan et al. 2005).
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