Selective ablation of retinoblastoma protein function by the RET finger protein.
The retinoblastoma tumor suppressor protein (Rb) affects gene transcription both negatively and positively and through this regulates distinct cellular responses. Although cell cycle regulation requires gene repression, Rb's ability to promote differentiation and part of its antiproliferative activity appears to rely on the activation of gene transcription. We present evidence here that the RET finger protein (RFP)/tripartite motif protein 27 (TRIM 27) inhibits gene transcription activation by Rb but does not affect gene repression. RFP binds to Rb and prevents the degradation of the EID-1 inhibitor of histone acetylation and differentiation. Furthermore, ablation of RFP in U2OS osteosarcoma cells augments a transcriptional program indicative of lineage-specific differentiation in response to Rb. These findings provide precedent for a regulatory pathway that uncouples different Rb-dependent activities and thus silences specific cellular responses to Rb in a selective way.
Krützfeldt
Maja
M
Centre for Cell and Molecular Biology, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB London, United Kingdom.
Ellis
Mark
M
Weekes
Daniel B
DB
Bull
Jonathan J
JJ
Eilers
Martin
M
Vivanco
Maria D M
MD
Sellers
William R
WR
Mittnacht
Sibylle
S
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D000070584:Tripartite Motif Proteins
D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005982:Glutathione Transferase; D008156:Luciferases; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C416925:EID1 protein, human; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins