IRF4
IRF4 is a master transcription factor of plasma cells and a protein myeloma cells cannot do without. Lenalidomide and its successors lower IRF4 by destroying the two factors, Ikaros and Aiolos, that keep it switched on.
Overview
IRF4 (chromosome 6p25.3) is a transcriptional activator that binds the interferon-stimulated response element of the MHC class I promoter and, with PU.1, the immunoglobulin lambda light-chain enhancer; it acts in lymphoid-specific signalling and, in complex with the BATF-JUNB heterodimer at AICE elements, in CD8 dendritic-cell differentiation (UniProt Q15306). In OnCo it is the downstream node of the immunomodulatory drugs: lenalidomide and golcadomide degrade Ikaros and Aiolos through cereblon, IRF4 and MYC fall, and the myeloma cell dies (lenalidomide mechanism steps).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · IRF4 is a master transcription factor of plasma cells and a protein myeloma cells cannot do without. Lenalidomide and its successors lower IRF4 by destroying the two factors, Ikaros and Aiolos, that keep it switched on.
- 1 · What it is
IRF4 is a master transcription factor of plasma cells and a protein myeloma cells cannot do without. Lenalidomide and its successors lower IRF4 by destroying the two factors, Ikaros and Aiolos, that keep it switched on.
- 2 · What goes wrong in cancer
IRF4 is not bound by any corpus drug; it is lowered as a consequence of Ikaros and Aiolos degradation, which is why it sits at the end of the immunomodulatory drug mechanism alongside MYC.
- 3 · How drugs use it
No product in this corpus aims at IRF4 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
External identifiers
Biology
IRF4 is not bound by any corpus drug; it is lowered as a consequence of Ikaros and Aiolos degradation, which is why it sits at the end of the immunomodulatory drug mechanism alongside MYC.
- Multiple myeloma (dependency; lowered by immunomodulatory drugs)
- Diffuse large B-cell lymphoma (golcadomide trials)
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery for this target: (TITLE:"IRF4" OR ABSTRACT:"IRF4" OR TITLE:"MUM1" OR ABSTRACT:"MUM1" OR TITLE:"LSIRF" OR ABSTRACT:"LSIRF" OR TITLE:"interferon regulatory factor 4" OR ABSTRACT:"interferon regulatory factor 4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about IRF4, not a curated reading list.
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