Journal article
ARF Directly Binds DP1: Interaction with DP1 Coincides with the G1 Arrest Function of ARF
Molecular and cellular biology, Vol.25(18), pp.8024-8036
09/2005
DOI: 10.1128/MCB.25.18.8024-8036.2005
PMCID: PMC1234342
PMID: 16135794
Abstract
The tumor suppressor ARF inhibits cell growth in response to oncogenic stress in a p53-dependent manner. Also, there is an increasing appreciation of ARF's ability to inhibit cell growth via multiple p53-independent mechanisms, including its ability to regulate the E2F pathway. We have investigated the interaction between the tumor suppressor ARF and DP1, the DNA binding partner of the E2F family of factors (E2Fs). We show that ARF directly binds to DP1. Interestingly, binding of ARF to DP1 results in an inhibition of the interaction between DP1 and E2F1. Moreover, ARF regulates the association of DP1 with its target gene, as evidenced by a chromatin immunoprecipitation assay with the
dhfr
promoter. By analyzing a series of ARF mutants, we demonstrate a strong correlation between ARF's ability to regulate DP1 and its ability to cause cell cycle arrest. S-phase inhibition by ARF is preceded by an inhibition of the E2F-activated genes. Moreover, we provide evidence that ARF inhibits the E2F-activated genes independently of p53 and Mdm2. Also, the interaction between ARF and DP1 is enhanced during oncogenic stress and “culture shock.” Taken together, our results show that DP1 is a critical direct target of ARF.
Details
- Title: Subtitle
- ARF Directly Binds DP1: Interaction with DP1 Coincides with the G1 Arrest Function of ARF
- Creators
- Abhishek Datta - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Jayita Sen - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Jussara Hagen - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Chandrashekhar K Korgaonkar - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Michael Caffrey - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Dawn E Quelle - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Douglas E Hughes - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Timothy J Ackerson - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Robert H Costa - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607Pradip Raychaudhuri - Department of Biochemistry and Molecular Genetics, 2302 MBRB (M/C 669), University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, Illinois 60607
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.25(18), pp.8024-8036
- DOI
- 10.1128/MCB.25.18.8024-8036.2005
- PMID
- 16135794
- PMCID
- PMC1234342
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 09/2005
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Neuroscience and Pharmacology
- Record Identifier
- 9984040490702771
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