Id and aging

Id1 is one of a family of helix-loop-helix (HLH) proteins that inhibits transcription by sequestering other HLH factors. It has been implicated in the regulation of cell growth and cellular aging. In the July 3 Proceedings of the National Academy of Sciences, Alani et al. provide genetic evidence supporting a role for Id1 in preventing cell aging (Proc Natl Acad Sci USA 2001, 98:7812-7816). They found that fibroblasts from Id1-null mice display premature senescence with increased expression of the cell-cycle regulators p16/INK4a, cyclin D1 and cyclin E. They show that Id1 specifically inhibits transcription of the p16/INK4a promoter, but does not affect p19/Arf regulation (although p19 is transcribed from the same locus as p16). Two E-box motifs in the p16/INK4a promoter are essential for Id1 repression. Finally, they report increased expression of p16/INK4a in vivo, in the ventral telencephalon of Id1-null embryos. The authors speculate that Id1 repression may be responsible for deregulation of p16 expression in the early stages of tumorigenesis.