BACKGROUND MUM1 (multiple myeloma 1)/IRF4 (also known as LSIRF, Pip, and ICSAT) is a member of the IRF family of transcriptional factors. It is considered to be a key regulator of several steps in lymphoid, myeloid, and dendritic cell differentiation and maturation. It is also an established marker of plasma cell differentiation. MUM1/IRF4 is normally expressed in plasma cells, a small percentage of germinal center (GC) B cells mainly located in the light zone, and activated T cells.1 Unlike other IRF-family members, MUM1/IRF4 is not induced by interferon, but rather by diverse mitogenic stimuli, including antigen receptor engagement, lipopolysaccharides, and CD40 signaling. These stimuli all activate the NF-κB pathway, which leads to MUM1/IRF4 promoter activation by NF-κB heterodimers. In addition, MUM1/IRF4 transcription can be activated by IL-4, implicating the STAT6 in its activation. The abundance of MUM1/IRF4 varies within the hematopoietic system in a lineage- and stage-specific manner. In mature B cells, MUM1/IRF4 expression is repressed by the Mitf transcription factor. In addition, MUM1/IRF4 is strongly expressed in multiple myeloma and several other lymphomas. Gene microarray analysis has further shown that the MUM1/IRF4 gene is preferentially clustered within the gene expression profile exhibited by activated B-like DLBCL, a subset of DLBCL associated with a worse prognosis. These studies implicate a significant role for MUM1/IRF4 in tumorigenesis and immune regulation. MUM1/IRF4 may be a promising target for the treatment of some of these neoplasms.2
For many genes, MUM1/IRF4 functions as a positive regulator of transcription, using its C-terminal transactivation domain. However, MUM1/IRF4 can repress the expression of some interferon-inducible genes by binding to interferon-stimulated response elements (ISREs) in their promoters, displacing the interferon-responsive IRF factors Irf1 and Irf2. MUM1/IRF4 can also repress other genes, such as BCL6, through as yet undefined mechanisms. Alone, MUM1/IRF4 binds DNA weakly due to its C-terminal autoinhibitory domain. However, MUM1/IRF4 can bind with high avidity to the 3′ enhancers of both κ and λ immunoglobulin light chains in conjunction with the ETS-family transcription factor PU.1 and the closely related factor SPIB. Moreover, additional protein-protein interactions between MUM1/IRF4 and other regulatory factors modulate its DNA-binding properties and/or transactivation potential. MUM1/IRF4 is an essential regulator at multiple steps in B-cell differentiation and plays a critical role in the adaptive immune responses of mature B cells. MUM1/IRF4 is also required for immunoglobulin class switch recombination (CSR). IRF4-deficient B cells fail to upregulate AID, the critical enzyme that mediates CSR. Outside the B-cell lineage, MUM1/IRF4 is essential for several stages of T-cell and myeloid-cell differentiation. IRF4 is emerging as a critical regulator of T-helper-cell differentiation, playing a required role in both Th2 and Th17 development by controlling cytokine expression and apoptosis. Mice deficient in MUM1/IRF4 exhibit impaired B- and T-cell function, absence of plasma cells with a drastic reduction in serum immunoglobulins, and an abrogated response to B-cell activation.3 However, MUM1/IRF4-deficient mice have no apparent phenotypes outside of the lymphoid and myeloid lineages, in keeping with the restricted expression of MUM1/IRF4 in these cell types. Therefore, potential therapies aimed at MUM1/IRF4 would have restricted and potentially manageable on-target toxicities within the hematopoietic system.4
1. Gualco, G. et al: Appl. Immunohistochem. Mol. Morphol. 18:301-10, 2010
2. Lu, R.: Trends Immunol. 29:487-92, 2008
3. Shaffer, A.L. et al: Clin. Cancer Res. 15:2954-61, 2009
4. Mudter, J. et al: J. Clin. Invest. 118:2415-26, 2008
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
Raised against recombinant human IRF4/MUM1 fragments expressed in E. coli.
Species & predicted
reactivity ( ):
IHC 1:50 - 1:200
Weight of protein:
Detects endogenous IRF4/MUM1 proteins without cross-reactivity with other family members.
Store at -20°C, 4°C for frequent use. Avoid repeated freeze-thaw cycles.
*Optimal working dilutions must be determined by end user.