Cooperative Nuclear Localization Sequences Lend a Novel Role to the N-Terminal Region of MSH6
| Autor: | Jill E. Clodfelter, Freddie R. Salsbury, Anita K. McCauley, Keith Bonin, Karin Scarpinato, Natalie R. Gassman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Nuclear Localization Signals
lcsh:Medicine Biophysics Simulations Conserved sequence 0302 clinical medicine Molecular cell biology Neoplasms Signaling in Cellular Processes lcsh:Science Conserved Sequence Sequence Deletion Genetics 0303 health sciences Multidisciplinary Protein subcellular localization prediction Nuclear Signaling Cell biology Nucleic acids DNA-Binding Proteins medicine.anatomical_structure 030220 oncology & carcinogenesis Research Article Signal Transduction Subcellular Fractions congenital hereditary and neonatal diseases and abnormalities Recombinant Fusion Proteins Green Fluorescent Proteins Molecular Sequence Data Biophysics Active Transport Cell Nucleus DNA repair Biology DNA-binding protein Models Biological 03 medical and health sciences Structure-Activity Relationship medicine NLS Humans Point Mutation Amino Acid Sequence neoplasms 030304 developmental biology Cell Nucleus lcsh:R nutritional and metabolic diseases Reproducibility of Results DNA Subcellular localization digestive system diseases Cell nucleus Kinetics lcsh:Q Nuclear transport Protein Multimerization Nuclear localization sequence |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 3, p e17907 (2011) |
| ISSN: | 1932-6203 |
| Popis: | Human mismatch repair proteins MSH2-MSH6 play an essential role in maintaining genetic stability and preventing disease. While protein functions have been extensively studied, the substantial amino-terminal region (NTR*) of MSH6 that is unique to eukaryotic proteins, has mostly evaded functional characterization. We demonstrate that a cluster of three nuclear localization signals (NLS) in the NTR direct nuclear import. Individual NLSs are capable of partially directing cytoplasmic protein into the nucleus; however only cooperative effects between all three NLSs efficiently transport MSH6 into the nucleus. In striking contrast to yeast and previous assumptions on required heterodimerization, human MSH6 does not determine localization of its heterodimeric partner, MSH2. A cancer-derived mutation localized between two of the three NLS significantly decreases nuclear localization of MSH6, suggesting altered protein localization can contribute to carcinogenesis. These results clarify the pending speculations on the functional role of the NTR in human MSH6 and identify a novel, cooperative nuclear localization signal. |
| Databáze: | OpenAIRE |
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