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Retinoblastoma protein represses transcription by recruiting a histone deacetylase
L Magnaghi-Jaulin1, R Groisman, I Naguibneva
1Laboratoire Oncogénèse, Différenciation et Transduction du Signal, CNRS UPR 9079, Villejuif, France.
Abstract:
The retinoblastoma tumour-suppressor protein Rb inhibits cell proliferation by repressing a subset of genes that are controlled by the E2F family of transcription factors and which are involved in progression from the G1 to the S phase of the cell cycle. Rb, which is recruited to target promoters by E2F1, represses transcription by masking the E2F1 transactivation domain and by inhibiting surrounding enhancer elements, an active repression that could be crucial for the proper control of progression through the cell cycle. Some transcriptional regulators act by acetylating or deacetylating the tails protruding from the core histones, thereby modulating the local structure of chromatin: for example, some transcriptional repressors function through the recruitment of histone deacetylases. We show here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb. In HDAC1, the sequence involved is an LXCXE motif, similar to that used by viral transforming proteins to contact Rb. Our results strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.
Insights
The retinoblastoma (Rb) protein interacts with histone deacetylase 1 (HDAC1) to control cell growth and differentiation. This Rb/HDAC1 complex is crucial for regulating the cell cycle and may be targeted by viruses.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The retinoblastoma (Rb) protein is a key tumor suppressor that inhibits cell proliferation.
- Rb represses specific genes regulated by E2F transcription factors, controlling G1 to S phase progression.
- Transcriptional regulators can modify chromatin structure through histone acetylation/deacetylation.
Purpose of the Study:
- To investigate the interaction between the Rb protein and histone deacetylase 1 (HDAC1).
- To determine the functional significance of the Rb/HDAC1 complex in cell proliferation and differentiation.
Main Methods:
- Co-immunoprecipitation assays to demonstrate physical interaction between Rb and HDAC1.
- Analysis of the LXCXE motif in HDAC1 for Rb binding.
- Functional assays to assess the role of the Rb/HDAC1 complex in cell cycle control.
Main Results:
- The histone deacetylase HDAC1 physically interacts with the Rb protein.
- An LXCXE motif in HDAC1 mediates its interaction with Rb, similar to viral oncoproteins.
- The Rb/HDAC1 complex plays a significant role in repressing gene transcription and controlling cell proliferation.
Conclusions:
- The Rb/HDAC1 complex is a critical component in regulating cell proliferation and differentiation.
- This complex represents a potential target for transforming viruses seeking to manipulate cell cycle control.