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Published on: January 7, 2019
A new component of the transcription factor DRTF1/E2F
R Girling1, J F Partridge, L R Bandara
1Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.
Abstract:
Transcription factor DRTF1/E2F coordinates events in the cell cycle with transcription by its cyclical interactions with important regulators of cellular proliferation like the retinoblastoma tumour-suppressor gene product (Rb) and the Rb-related protein, p107 (refs 1-8). DRTF1/E2F binding sites occur in the control regions of genes involved in proliferation, and both Rb and p107 repress the capacity of DRTF1/E2F to activate transcription (refs 11, 12; M. Zamanian and N.B.L.T., manuscript submitted). Mutant Rb proteins isolated from tumour cells are unable to bind DRTF1/E2F (refs 11-13), and certain viral oncoproteins, such as adenovirus E1A, sequester Rb and p107 in order to free active DRTF1/E2F (refs 5, 11, 12, 14, 15). Here we report the isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1), a major sequence-specific binding protein that is present in DRTF1/E2F, including Rb- and p107-associated DRTF1/E2F. The DNA-binding domain of DP-1 contains a region that resembles that of E2F-1 (refs 16, 17), and recognizes the same sequence. DRTF1/E2F thus appears to contain at least two sequence-specific DNA-binding proteins.
Insights
Researchers identified a new protein, DP-1, which is a key component of the DRTF1/E2F transcription factor complex. This finding reveals that DRTF1/E2F includes at least two distinct DNA-binding proteins, impacting cell cycle regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Transcription factor DRTF1/E2F regulates cell cycle and proliferation.
- DRTF1/E2F interacts with retinoblastoma tumor-suppressor gene product (Rb) and p107.
- Rb and p107 binding inhibits DRTF1/E2F transcriptional activity.
Purpose of the Study:
- To isolate and characterize novel components of the DRTF1/E2F complex.
- To understand the molecular basis of DRTF1/E2F's role in cell cycle control.
Main Methods:
- Complementary DNA (cDNA) isolation.
- Protein identification and characterization.
- DNA-binding assays.
Main Results:
- Isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1).
- DP-1 is a major sequence-specific DNA-binding protein within DRTF1/E2F.
- DP-1's DNA-binding domain is similar to E2F-1 and recognizes the same DNA sequence.
Conclusions:
- DRTF1/E2F comprises at least two distinct sequence-specific DNA-binding proteins.
- DP-1 is a crucial component of the DRTF1/E2F complex.
- This discovery enhances understanding of cell cycle transcriptional regulation.
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