Proteomic Analyses Uncover a New Function and Mode of Action for Mouse Homolog of Diaphanous 2 (mDia2)
| Autor: | Isogai, Tadamoto, Van Der Kammen, Rob, Goerdayal, Soenita S., Heck, Albert J. R., Altelaar, A. F. Maarten, Innocenti, Metello, Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics |
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| Přispěvatelé: | Isogai, T, van der Kammen, R, Goerdayal, S, Heck, A, Altelaar, A, Innocenti, M, Sub Biomol.Mass Spect. and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics |
| Rok vydání: | 2015 |
| Předmět: |
gain of function mutation
p53 Fetal Proteins Proteomics cell migration Protein Conformation protein p53 Cellular differentiation Apoptosis mouse homolog of diaphanous 2 protein binding Biochemistry Interactome F-box protein Chromatography Affinity Mass Spectrometry Analytical Chemistry Mice caspase 7 0302 clinical medicine Ubiquitin mDia2 caspase 3 Taverne Cell polarity Protein Interaction Maps Cytoskeleton proteomic 0303 health sciences conformational transition Microfilament Proteins apoptosis article Nuclear Proteins cell signalling protein function unclassified drug Cell biology cell polarity regulator protein priority journal protein protein interaction 030220 oncology & carcinogenesis Formins Gene Knockdown Techniques transcription regulation down regulation Microtubule-Associated Proteins Protein Binding autophagy actin filament formin cell motility Biology ubiquitination loss of function mutation 03 medical and health sciences proteomics cancer Animals Humans protein expression Molecular Biology Actin 030304 developmental biology Sequence Homology Amino Acid F-Box Proteins Research NADPH Dehydrogenase Reproducibility of Results protein analysis biology.protein Tumor Suppressor Protein p53 Cytokinesis DNA Damage HeLa Cells |
| Zdroj: | Molecular & Cellular Proteomics : MCP Molecular & Cellular Proteomics, 14(4), 1064. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 1535-9476 |
| DOI: | 10.6084/m9.figshare.1554820.v1 |
| Popis: | mDia2 is an auto-inhibited Formin influencing actin dynamics upon conversion to the active conformation. mDia2 regulates actin-based protrusions and cell invasion, cell differentiation, vesicle trafficking, and cytokinesis. However, whether mDia2 has additional functions and how its action is functionally specified remain unknown. Here we draw the interactome of auto-inhibited and constitutively active mDia2 to address these issues. We embed mDia2 in protein networks accounting for its attributed functions and unexpectedly link it to the Ubiquitin Proteasome System. Taking FBXO3 as a test case, we show that mDia2 binds FBXO3 and p53, and regulates p53 transcriptional activity in an actin-nucleation-independent and conformation-insensitive manner. Increased mDia2 and FBXO3 levels elevate p53 activity and expression thereby sensitizing cells to p53-dependent apoptosis, whereas their decrease produces opposite effects. Thus, we discover a new role of mDia2 in p53 regulation suggesting that the closed conformation is biologically active and an FBXO3-based mechanism to functionally specify mDia2’s activity. |
| Databáze: | OpenAIRE |
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