Intrinsic Negative Cell Cycle Regulation Provided by PIP Box- and Cul4Cdt2-Mediated Destruction of E2f1 during S Phase
| Autor: | Robert J. Duronio, Aida Flor A. de la Cruz, Bruce A. Edgar, Vuong Tran, Tânia Reis, Shusaku Shibutani, William J. Turbyfill |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
DNA Replication
endocrine system Amino Acid Motifs DEVBIO CELLCYCLE Models Biological Retinoblastoma Protein General Biochemistry Genetics and Molecular Biology Article S Phase 03 medical and health sciences 0302 clinical medicine Cyclin-dependent kinase Proliferating Cell Nuclear Antigen E2F1 Humans Animals Drosophila Proteins Amino Acid Sequence Phosphorylation E2F Molecular Biology 030304 developmental biology 0303 health sciences Stem Cell Factor biology Sequence Homology Amino Acid Cell growth Ubiquitin Cell Cycle Retinoblastoma protein Temperature Cell Biology DNA Cell cycle Cullin Proteins 3. Good health Ubiquitin ligase Cell biology Drosophila melanogaster Gene Expression Regulation 030220 oncology & carcinogenesis biology.protein biological phenomena cell phenomena and immunity E2F Transcription Factors E2F1 Transcription Factor Protein Binding Developmental Biology |
| Zdroj: | Developmental Cell. 15(6):890-900 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2008.10.003 |
| Popis: | Summary E2F transcription factors are key regulators of cell proliferation that are inhibited by pRb family tumor suppressors. pRb-independent modes of E2F inhibition have also been described, but their contribution to animal development and tumor suppression is unclear. Here, we show that S phase-specific destruction of Drosophila E2f1 provides a novel mechanism for cell cycle regulation. E2f1 destruction is mediated by a PCNA-interacting-protein (PIP) motif in E2f1 and the Cul4 Cdt2 E3 ubiquitin ligase and requires the Dp dimerization partner but not direct Cdk phosphorylation or Rbf1 binding. E2f1 lacking a functional PIP motif accumulates inappropriately during S phase and is more potent than wild-type E2f1 at accelerating cell cycle progression and inducing apoptosis. Thus, S phase-coupled destruction is a key negative regulator of E2f1 activity. We propose that pRb-independent inhibition of E2F during S phase is an evolutionarily conserved feature of the metazoan cell cycle that is necessary for development. |
| Databáze: | OpenAIRE |
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