The protein hSnm1B is stabilized when bound to the telomere-binding protein TRF2.
hSnm1B is member of the SNM family of exonucleases involved in DNA processing and is known to be localized to telomeres via binding to the telomere-binding protein TRF2. Here we demonstrate that the C terminus of hSnm1B facilitates the concentration of hSnm1B on telomeres by promoting ubiquitin-mediated degradation of hSnm1B that is not localized to telomeres, as well as by blocking protein degradation and fostering localization to telomeres via binding of TRF2. Finally, a mutant of hSnm1B stabilized independently of exogenous TRF2-induced cell death. Taken together, we speculate that sequestering hSnm1B at telomeres by a combination of stabilizing the protein when bound to telomeres and degrading it when not bound to telomeres may be a means to prevent potentially lethal effects of unregulated hSnm1B activity.
Freibaum
Brian D
BD
Departments of Pharmacology and Cancer Biology and Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Counter
Christopher M
CM
D016923:Cell Death / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D016615:Telomere / Q000201:enzymology* / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
D009687:Nuclear Proteins; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D025801:Ubiquitin; C493741:DCLRE1B protein, human; D005090:Exodeoxyribonucleases; D046988:Proteasome Endopeptidase Complex; D045643:DNA Repair Enzymes