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.
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Authors | Kathleen Richter, Sukhdev Brar, Madhumita Ray, Prapaporn Pisitkun, Silvia Bolland, Laurent Verkoczy, Marilyn Diaz |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 284
Issue 44
Pg. 30652-61
(Oct 30 2009)
ISSN: 1083-351X [Electronic] United States |
PMID | 19734146
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- Neoplasm Proteins
- Nuclear Proteins
- AICDA (activation-induced cytidine deaminase)
- Cytidine Deaminase
- GTP Phosphohydrolases
- NUGGC protein, human
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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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