Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product.
The protein encoded by the retinoblastoma susceptibility gene (Rb) functions as a tumour suppressor and negative growth regulator. As actively growing cells require the ongoing synthesis of ribosomal RNA, we considered that Rb might interact with the ribosomal DNA transcription apparatus. Here we report that (1) there is an accumulation of Rb protein in the nucleoli of differentiated U937 cells which correlates with inhibition of rDNA transcription; (2) addition of Rb to an in vitro transcription system inhibits transcription by RNA polymerase I; (3) this inhibition requires a functional Rb pocket; and (4) Rb specifically inhibits the activity of the RNA polymerase I transcription factor UBF (upstream binding factor) in vitro. This last observation was confirmed by affinity chromatography and immunoprecipitation, which demonstrated an interaction between Rb and UBF. These results indicate that there is an additional mechanism by which Rb suppresses cell growth, namely that Rb directly represses transcription of the rRNA genes.
Cavanaugh
A H
AH
Sigfried and Janet Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2618.
Hempel
W M
WM
Taylor
L J
LJ
Rogalsky
V
V
Todorov
G
G
Rothblum
L I
LI
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D004275:DNA, Ribosomal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins; D011233:Precipitin Tests; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors*; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C063844:transcription factor UBF; D012318:RNA Polymerase I