期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 17, 页码 6847-6852出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1220751110
关键词
cellular biology; cancer; autoimmunity; juvenile arthritis
资金
- William D. Robinson Fellowship from the Arthritis Foundation/Michigan Chapter
- START program of the Faculty of Medicine, RWTH Aachen
- Arthritis Foundation
- German Research Foundation through Research Training Group [1331]
- National Institutes of Health [R03 AR-056748-01, K01 AR-055620, R01 AI062248, R01 AI087128]
- University of Michigan Tumor Immunology Training Program Grant [T32-CA-88784-03]
- University of Michigan Rheumatic Disease Core Center Grant [5-P30-AR-048310-07]
- University of Michigan Postdoctoral Translational Scholars Program Grant [UL1-RR-024986]
- Excellence Initiative of the German federal government
- Excellence Initiative of the German state government
- Burroughs Wellcome Fund Clinical Scientist Award in Translational Research
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.
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