Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types.
MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, Bcl10. Bcl10 is a cellular homolog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-kappaB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappaB but did not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy.
Willis
T G
TG
Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Jadayel
D M
DM
Du
M Q
MQ
Peng
H
H
Perry
A R
AR
Abdul-Rauf
M
M
Price
H
H
Karran
L
L
Majekodunmi
O
O
Wlodarska
I
I
Pan
L
L
Crook
T
T
Hamoudi
R
R
Isaacson
P G
PG
Dyer
M J
MJ
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001483:Base Sequence; D019556:COS Cells; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic