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Speckled-like pattern in the germinal center (SLIP-GC), a nuclear GTPase expressed in activation-induced deaminase-expressing lymphomas and germinal center B cells.

Abstract
We identified a novel GTPase, SLIP-GC, with expression limited to a few tissues, in particular germinal center B cells. It lacks homology to any known proteins, indicating that it may belong to a novel family of GTPases. SLIP-GC is expressed in germinal center B cells and in lymphomas derived from germinal center B cells such as large diffuse B cell lymphomas. In cell lines, SLIP-GC is expressed in lymphomas that express activation-induced deaminase (AID) and that likely undergo somatic hypermutation. SLIP-GC is a nuclear protein, and it localizes to replication factories. Reduction of SLIP-GC levels in the Burkitt lymphoma cell line Raji and in non-Hodgkin lymphoma cell lines resulted in an increase in DNA breaks and apoptosis that was AID-dependent, as simultaneous reduction of AID abrogated the deleterious effects of SLIP-GC reduction. These results strongly suggest that SLIP-GC is a replication-related protein in germinal center B cells whose reduction is toxic to cells through an AID-dependent mechanism.
AuthorsKathleen Richter, Sukhdev Brar, Madhumita Ray, Prapaporn Pisitkun, Silvia Bolland, Laurent Verkoczy, Marilyn Diaz
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 44 Pg. 30652-61 (Oct 30 2009) ISSN: 1083-351X [Electronic] United States
PMID19734146 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
Chemical References
  • Neoplasm Proteins
  • Nuclear Proteins
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase
  • GTP Phosphohydrolases
  • NUGGC protein, human
Topics
  • Apoptosis
  • B-Lymphocytes (chemistry, pathology)
  • Cell Line, Tumor
  • Cytidine Deaminase (analysis)
  • DNA Damage
  • GTP Phosphohydrolases (analysis, physiology)
  • Germinal Center (chemistry, pathology)
  • Humans
  • Lymphoma, B-Cell (chemistry, pathology)
  • Neoplasm Proteins
  • Nuclear Proteins (analysis, physiology)
  • Tissue Distribution

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