Intercellular trafficking of the nuclear oncoprotein DEK
Author(s)Ploegh, Hidde; Saha, Anjan K.; Kappes, Ferdinand; Mundade, Amruta; Deutzmann, Anja; Rosmarin, David M.; Legendre, Maureen; Chatain, Nicolas; Al-Obaidi, Zeina; Adams, Barbara S.; Ferrando-May, Elisa; Mor-Vaknin, Nirit; Markovitz, David M.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
Saha, A. K., F. Kappes, A. Mundade, A. Deutzmann, D. M. Rosmarin, M. Legendre, N. Chatain, et al. “Intercellular trafficking of the nuclear oncoprotein DEK.” Proceedings of the National Academy of Sciences 110, no. 17 (April 23, 2013): 6847-6852.
Final published version