title: Intercellular trafficking of the nuclear oncoprotein DEK.
abstract: DEK is a biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity. In addition, DEK can be secreted and function as a chemotactic, proinflammatory factor. Here we show that exogenous DEK can penetrate cells, translocate to the nucleus, and there carry out its endogenous nuclear functions. Strikingly, adjacent cells can take up DEK secreted from synovial macrophages. DEK internalization is a heparan sulfate-dependent process, and cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits, the phenotypic aberrations characteristic of these cells. These findings thus unify the extracellular and intracellular activities of DEK, and suggest that this paracrine loop involving DEK plays a role in chromatin biology.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Anjan K
authors.initials: AK
authors.lastname: Saha
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Kappes
authors.forename: Amruta
authors.initials: A
authors.lastname: Mundade
authors.forename: Anja
authors.initials: A
authors.lastname: Deutzmann
authors.forename: David M
authors.initials: DM
authors.lastname: Rosmarin
authors.forename: Maureen
authors.initials: M
authors.lastname: Legendre
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chatain
authors.forename: Zeina
authors.initials: Z
authors.lastname: Al-Obaidi
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Adams
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferrando-May
authors.forename: Nirit
authors.initials: N
authors.lastname: Mor-Vaknin
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
mesh_terms: D002458:Cell Fractionation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D015513:Oncogene Proteins / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D021381:Protein Transport / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D006570:Heterochromatin; D006657:Histones; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D034741:RNA, Small Interfering