PRb2/p130 and p107 control cell growth by multiple strategies and in association with different compartments within the nucleus.

Abstract

It has been recently reported that retinoblastoma family proteins suppress cell growth by regulating not only E2F-dependent mRNA transcription but also rRNA and tRNA transcription and, through HDAC1 recruitment, chromatin packaging. In the present study we report data showing that these various control strategies are correlated, at least in part, with nuclear compartmentalization of retinoblastoma proteins. In a first series of experiments, we showed that pRb2/p130 and p107 are not evenly distributed within the nucleus and that cell cycle-dependent binding with E2F4 changes also as a function of their subnuclear localization. Namely, in the nucleoplasm pRb2/p130-E2F4 complexes are more numerous during G0/G1 while in the nucleolus they increase in S phase. Partially different functions for p107 are suggested since p107-E2F4 complexes in the nucleoplasm are more numerous is S phase with respect to G0/G1 and no cell cycle change is observed in the nucleolus. In a second series of experiments we showed that pRb2/p130, p107, E2F4, and pRb2/p130-HDAC1 complexes are all inner nuclear matrix-associated proteins and localize to sites different from pRb/p105 ones. We provide further evidence of multiple and partially distinct retinoblastoma protein family functional roles during cell cycle. Moreover, our data support emerging evidence for functional interrelationships between nuclear structure and gene expression.