| General information | Literature | Expression | Regulation | Mutation | Interaction |
|
Basic Information |
|
|---|---|
Gene ID | 3662 |
Name | IRF4 |
Synonymous | LSIRF|MUM1|NF-EM5|SHEP8;interferon regulatory factor 4;IRF4;interferon regulatory factor 4 |
Definition | lymphocyte-specific interferon regulatory factor|multiple myeloma oncogene 1 |
Position | 6p25-p23 |
Gene type | protein-coding |
|
Title |
Abstract |
| IRF4 is a suppressor of c-Myc induced B cell leukemia. | Interferon regulatory factor 4 (IRF4) is a critical transcriptional regulator in B cell development and function. We have previously shown that IRF4, together with IRF8, orchestrates pre-B cell development by limiting pre-B cell expansion and by promoting pre-B cell differentiation. Here, we report that IRF4 suppresses c-Myc induced leukemia in EmuMyc mice. Our results show that c-Myc induced leukemia was greatly accelerated in the IRF4 heterozygous mice (IRF4(+/-)Myc); the average age of mortality in the IRF4(+/-)Myc mice was only 7 to 8 weeks but was 20 weeks in the control mice. Our results show that IRF4(+/-)Myc leukemic cells were derived from large pre-B cells and were hyperproliferative and resistant to apoptosis. Further analysis revealed that the majority of IRF4(+/-)Myc leukemic cells inactivated the wild-type IRF4 allele and contained defects in Arf-p53 tumor suppressor pathway. p27(kip) is part of the molecular circuitry that controls pre-B cell expansion. Our results show that expression of p27(kip) was lost in the IRF4(+/-)Myc leukemic cells and reconstitution of IRF4 expression in those cells induced p27(kip) and inhibited their expansion. Thus, IRF4 functions as a classical tumor suppressor to inhibit c-Myc induced B cell leukemia in EmuMyc mice. |