Active nuclear import and cytoplasmic retention of activation-induced deaminase
dc.contributor.author | Patenaude, Anne-Marie | |
dc.contributor.author | Orthwein, Alexandre | |
dc.contributor.author | Hu, Yi | |
dc.contributor.author | Campo, Vanina A. | |
dc.contributor.author | Kavli, Bodil | |
dc.contributor.author | Buschiazzo, Alejandro | |
dc.contributor.author | Di Noia, Javier Marcelo | |
dc.date.accessioned | 2009-11-24T20:45:35Z | |
dc.date.available | 2009-11-24T20:45:35Z | |
dc.date.issued | 2009 | |
dc.identifier.uri | http://hdl.handle.net/1866/3196 | |
dc.description.sponsorship | This work was supported by the Canadian Institutes of Health Research (MOP 84543) and a Canada Research Chair (to J.M.D.). A.O. was supported by a fellowship from the Canadian Institutes of Health Research Cancer Training Program at the IRCM. V.A.C. was supported in part by a Michel Saucier fellowship from the Louis-Pasteur Canadian Fund through the University of Montreal. | en |
dc.subject.mesh | Active Transport, Cell Nucleus | en |
dc.subject.mesh | Cell Nucleus/enzymology | en |
dc.subject.mesh | Cytidine Deaminase/chemistry | en |
dc.subject.mesh | Cytidine Deaminase/metabolism | en |
dc.subject.mesh | Diffusion | en |
dc.subject.mesh | HeLa Cells | en |
dc.subject.mesh | Humans | en |
dc.subject.mesh | Models, Molecular | en |
dc.subject.mesh | Nuclear Localization Signals | en |
dc.subject.mesh | Protein Binding | en |
dc.subject.mesh | Protein Conformation | en |
dc.subject.mesh | Protein Structure, Tertiary | en |
dc.subject.mesh | Subcellular Fractions/enzymology | en |
dc.subject.mesh | alpha Karyopherins/metabolism | en |
dc.title | Active nuclear import and cytoplasmic retention of activation-induced deaminase | en |
dc.type | Article | en |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. Département de médecine | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. Institut de recherches cliniques de Montréal | fr |
dc.identifier.doi | 10.1038/nsmb.1598 | |
dcterms.abstract | The enzyme activation-induced deaminase (AID) triggers antibody diversification in B cells by catalyzing deamination and consequently mutation of immunoglobulin genes. To minimize off-target deamination, AID is restrained by several regulatory mechanisms including nuclear exclusion, thought to be mediated exclusively by active nuclear export. Here we identify two other mechanisms involved in controlling AID subcellular localization. AID is unable to passively diffuse into the nucleus, despite its small size, and its nuclear entry requires active import mediated by a conformational nuclear localization signal. We also identify in its C terminus a determinant for AID cytoplasmic retention, which hampers diffusion to the nucleus, competes with nuclear import and is crucial for maintaining the predominantly cytoplasmic localization of AID in steady-state conditions. Blocking nuclear import alters the balance between these processes in favor of cytoplasmic retention, resulting in reduced isotype class switching. | en |
dcterms.language | eng | en |
UdeM.VersionRioxx | Version acceptée / Accepted Manuscript | |
oaire.citationTitle | Nature structural and molecular biology | |
oaire.citationVolume | 16 | |
oaire.citationIssue | 5 | |
oaire.citationStartPage | 517 | |
oaire.citationEndPage | 527 |
Files in this item
This item appears in the following Collection(s)
This document disseminated on Papyrus is the exclusive property of the copyright holders and is protected by the Copyright Act (R.S.C. 1985, c. C-42). It may be used for fair dealing and non-commercial purposes, for private study or research, criticism and review as provided by law. For any other use, written authorization from the copyright holders is required.