C-FOS is an integral component of the IKZF1 transactivator complex and mediates lenalidomide resistance in multiple myeloma.

ABSTRACT:

Background

The immunomodulatory drug lenalidomide, which is now widely used for the treatment of multiple myeloma (MM), exerts pharmacological action through the ubiquitin-dependent degradation of IKZF1 and subsequent down-regulation of interferon regulatory factor 4 (IRF4), a critical factor for the survival of MM cells. IKZF1 acts principally as a tumour suppressor via transcriptional repression of oncogenes in normal lymphoid lineages. In contrast, IKZF1 activates IRF4 and other oncogenes in MM cells, suggesting the involvement of unknown co-factors in switching the IKZF1 complex from a transcriptional repressor to an activator. The transactivating components of the IKZF1 complex might promote lenalidomide resistance by residing on regulatory regions of the IRF4 gene to maintain

SUBMITTER: Osada N 

PROVIDER: S-EPMC10426395 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature