Speckled-like pattern in the germinal center (SLIP-GC), a nuclear GTPase expressed in activation-induced deaminase-expressing lymphomas and germinal center B cells.
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.
Richter
Kathleen
K
Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Brar
Sukhdev
S
Ray
Madhumita
M
Pisitkun
Prapaporn
P
Bolland
Silvia
S
Verkoczy
Laurent
L
Diaz
Marilyn
M
D017209:Apoptosis; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000032:analysis*; D004249:DNA Damage; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000502:physiology*; D018858:Germinal Center / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000473:pathology; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D014018:Tissue Distribution; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D020558:GTP Phosphohydrolases; C545443:NUGGC protein, human