title: The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin homeostasis and nuclear pore complex function.
abstract: Nuclear pore complexes are composed of ∼30 different proteins, each present at the pore in multiple copies. Together these proteins create specialized channels that convey cargo between the cytoplasm and the nuclear interior. With the building blocks of nuclear pores identified, one challenge is to decipher how these proteins are coordinately produced and assembled into macromolecular pore structures with each cell division. Specific individual pore proteins and protein cofactors have been probed for their role in the assembly process, as well as certain kinases that add a layer of regulation via the phosphorylation status of nucleoporins. Other posttranslational modifications are candidates for coordinating events of pore assembly as well. In this study of two pore-associated small ubiquitin-like modifier (SUMO) proteases, sentrin/SUMO-specific protease 1 (SENP1) and SENP2, we observe that many nucleoporins are mislocalized and, in some cases, reduced in level when SENP1 and SENP2 are codepleted. The pore complexes present under these conditions are still capable of transport, although the kinetics of specific cargo is altered. These results reveal a new role for the pore-associated SENPs in nucleoporin homeostasis and in achieving proper configuration of the nuclear pore complex.
authors.affiliation: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112 Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Kin-Hoe
authors.initials: KH
authors.lastname: Chow
authors.forename: Suzanne
authors.initials: S
authors.lastname: Elgort
authors.forename: Mary
authors.initials: M
authors.lastname: Dasso
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Powers
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Ullman
mesh_terms: D021581:Active Transport, Cell Nucleus; D003546:Cysteine Endopeptidases / Q000502:physiology*; D010450:Endopeptidases / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007399:Interphase; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022022:Nuclear Pore / Q000502:physiology*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; C094157:POM121 protein, human; D034741:RNA, Small Interfering; C506117:SUN1 protein, human; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human