title: Ubiquitylation-dependent downregulation of Nck regulates its functional activity.
abstract: The Nck adapter protein is involved in key cellular functions, such as actin polymerization and reorganization, serving as a molecular bridge between the surface complex essential for foreign antigen recognition, the T-cell antigen receptor (TCR), and the actin machinery. However, the mechanisms regulating Nck expression and functions are unknown. In this study, we revealed Nck negative regulation and demonstrated that Nck is ubiquitylated following cellular activation. We identified the molecular determinants and mediators involved in this process. Our data suggest that Nck ubiquitylation might serve as a mechanism controlling Nck-mediated effector functions during cellular activation.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Noah
authors.initials: N
authors.lastname: Joseph
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Reicher
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Ahuvit
authors.initials: A
authors.lastname: David
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Matalon
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: Mira.Barda-Saad@biu.ac.il.
authors.forename: Mira
authors.initials: M
authors.lastname: Barda-Saad
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D015536:Down-Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054875:Ubiquitination; D018909:src Homology Domains
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D050721:Proto-Oncogene Proteins c-cbl; D046988:Proteasome Endopeptidase Complex
keywords: Actin machinery; Nck; T-cell signaling; Ubiquitylation