Expression of the Leo1-like domain of replicative senescence down-regulated Leo1-like (RDL) protein promotes senescence of 2BS fibroblasts.

Replicative senescence is thought to relate to aging in vivo and tumor suppression. In this report, we isolated a gene and designated it as RDL (replicative senescence down-regulated Leo1-like gene). RDL's expression decreased upon replicative senescence of human diploid 2BS fibroblasts. Overexpression of RDL slightly delayed 2BS fibroblast senescence, whereas suppression of RDL expression imposed no obvious effects on senescence. However, introduction of cDNA fragment encoding the Leo1-like domain of RDLp (Leo) alone shortened the replicative life span of 2BS fibroblasts and promoted several senescent features; the introduction of truncated RDL cDNA fragment resulting from deletion of Leo (RDL-Leo-) significantly prolonged 2BS life span and caused a noticeable delay of these senescent features. We demonstrated that introduction of Leo obviously increased the expression of p16INK4a, p21WAF1, and PTEN, whereas introduction of RDL-Leo- distinctly decreased p16INK4a expression. Taken together, our results suggest that the Leo1-like domain of RDLp is a senescence-associated domain that accelerates the senescence of 2BS fibroblasts and that there should be another counteractive domain in the remaining part of RDLp.