title: Human TREX2 components PCID2 and centrin 2, but not ENY2, have distinct functions in protein export and co-localize to the centrosome.
abstract: TREX-2 is a five protein complex, conserved from yeast to humans, involved in linking mRNA transcription and export. The centrin 2 subunit of TREX-2 is also a component of the centrosome and is additionally involved in a distinctly different process of nuclear protein export. While centrin 2 is a known multifunctional protein, the roles of other human TREX-2 complex proteins other than mRNA export are not known. In this study, we found that human TREX-2 member PCID2 but not ENY2 is involved in some of the same cellular processes as those of centrin 2 apart from the classical TREX-2 function. PCID2 is present at the centrosome in a subset of HeLa cells and this localization is centrin 2 dependent. Furthermore, the presence of PCID2 at the centrosome is prevalent throughout the cell cycle as determined by co-staining with cyclins E, A and B. PCID2 but not ENY2 is also involved in protein export. Surprisingly, siRNA knockdown of PCID2 delayed the rate of nuclear protein export, a mechanism distinct from the effects of centrin 2, which when knocked down inhibits export. Finally we showed that co-depletion of centrin 2 and PCID2 leads to blocking rather than delaying nuclear protein export, indicating the dominance of the centrin 2 phenotype. Together these results represent the first discovery of specific novel functions for PCID2 other than mRNA export and suggest that components of the TREX-2 complex serve alternative shared roles in the regulation of nuclear transport and cell cycle progression.
authors.affiliation: Westminster College, Department of Biology, 319 South Market Street, New Wilmington, PA 16172, USA.
authors.forename: Corey N
authors.initials: CN
authors.lastname: Cunningham
authors.affiliation: Westminster College, Department of Biology, 319 South Market Street, New Wilmington, PA 16172, USA.
authors.forename: Casey A
authors.initials: CA
authors.lastname: Schmidt
authors.affiliation: Westminster College, Department of Biology, 319 South Market Street, New Wilmington, PA 16172, USA.
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Schramm
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California - San Diego, 9500 Gilman Drive, #0347, La Jolla, CA 92093-0347, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Gaylord
authors.affiliation: Westminster College, Department of Biology, 319 South Market Street, New Wilmington, PA 16172, USA. Electronic address: resendkk@westminster.edu.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Resendes
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000037:antagonists & inhibitors / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: C472752:CETN2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C527171:Eny2 protein, human; D009687:Nuclear Proteins; C586854:PCID2 protein, human; D010750:Phosphoproteins; D021122:Protein Subunits; D034741:RNA, Small Interfering; D014157:Transcription Factors; D005090:Exodeoxyribonucleases; C486104:TREX2 protein, human
keywords: Centrin 2; Centrosome; ENY2; Nuclear protein export; PCID2; TREX-2