title: TR3 orphan receptor is expressed in vascular endothelial cells and mediates cell cycle arrest.
abstract: OBJECTIVE
  Endothelial cells play a pivotal role in vascular homeostasis. In this study, we investigated the function of the nerve growth factor-induced protein-B (NGFI-B) subfamily of nuclear receptors comprising the TR3 orphan receptor (TR3), mitogen-induced nuclear orphan receptor (MINOR), and nuclear orphan receptor of T cells (NOT) in endothelial cells.
  
  
  RESULTS
  The mRNA expression of TR3, MINOR, and NOT in atherosclerotic lesions was assessed in human vascular specimens. Each of these factors is expressed in smooth muscle cells, as described before, and in subsets of endothelial cells, implicating that they might affect endothelial cell function. Adenoviral overexpression of TR3 in cultured endothelial cells resulted in decreased [3H]thymidine incorporation, whereas a dominant-negative TR3 variant that inhibits the activity of endogenous TR3-like factors enhanced DNA synthesis. TR3 interfered with progression of the cell cycle by upregulating p27Kip1 and downregulating cyclin A, whereas expression levels of a number of other cell cycle-associated proteins remained unchanged.
  
  
  CONCLUSIONS
  These findings demonstrate that TR3 is a modulator of endothelial cell proliferation and arrests endothelial cells in the G1 phase of the cell cycle by influencing cell cycle protein levels. We hypothesize involvement of TR3 in the maintenance of integrity of the vascular endothelium.
authors.affiliation: Department of Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: E Karin
authors.initials: EK
authors.lastname: Arkenbout
authors.forename: Maaike
authors.initials: M
authors.lastname: van Bragt
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Chris
authors.initials: C
authors.lastname: van Bree
authors.forename: Jos M
authors.initials: JM
authors.lastname: Grimbergen
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.forename: Hans
authors.initials: H
authors.lastname: Pannekoek
authors.forename: Carlie J M
authors.initials: CJ
authors.lastname: de Vries
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010455:Peptides / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D011987:Receptors, Steroid / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion / Q000235:genetics; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism / Q000821:virology; D015533:Transcriptional Activation / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology / Q000821:virology; D014779:Virus Replication / Q000235:genetics
chemical_list: D018076:DNA, Complementary; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010455:Peptides; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone