title: RB [corrected] as a modulator of transcription.
abstract: pRB interacts with a number of transcription factors and can both directly and indirectly modulate transcriptional activity. Growth suppression by pRB is tightly linked to its ability to form complexes with E2F which are capable of repressing transcription of certain genes required for S phase. The ability of pRB to enhance the activity of several non-E2F transcription factors might suggest a mechanism by which pRB could coordinately regulate sets of genes at or near the restriction point. Specifically, complexes consisting of underphosphorylated pRB and E2F, by virtue of transcriptional repression of promoters containing E2F sites, would act to block entry into S phase. At the same time, distinct complexes of underphosphorylated pRB and transcription factors such as the glucocorticoid receptor, ATF-2, or MyoD, might lead to an increase in the transcription of genes required for differentiation or for additional growth inhibitory functions (e.g. TGF-beta 1). Changes in the activities of various cyclin-dependent kinase complexes would lead to phosphorylation of pRB and thus coordinate a release of S phase genes from repression with a loss of activation of differentiation genes. While this model is speculative, the role of pRB as a transcriptional modulator, as well as its interactions with cell-cycle regulatory kinases, places it in a position to integrate extracellular and intracellular growth signals and to transduce those signals into changes in gene transcription which ultimately influence cell growth and differentiation.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Sellers
authors.forename: W G
authors.initials: WG
authors.lastname: Kaelin
mesh_terms: D006801:Humans; D012318:RNA Polymerase I / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D016160:Retinoblastoma Protein; D012319:RNA Polymerase II; D012318:RNA Polymerase I