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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.

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

The Journal of biological chemistry (2009-09-08)
Kathleen Richter, Sukhdev Brar, Madhumita Ray, Prapaporn Pisitkun, Silvia Bolland, Laurent Verkoczy, Marilyn Diaz
RÉSUMÉ

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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