Asset Details
Do you wish to reserve the book?
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells
Do you wish to request the book?
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Interferon regulatory factor 4 mediates nonenzymatic IRE1 dependency in multiple myeloma cells
2025
Overview
Multiple myeloma (MM) arises through oncogenic transformation of immunoglobulin-secreting plasma cells. MM often co-opts the central endoplasmic reticulum (ER)-stress mitigator, inositol-requiring enzyme 1 (IRE1), to sustain malignant growth. While certain MMs require enzymatic IRE1-dependent activation of the transcription factor XBP1s, others display a nonenzymatic IRE1 dependency that is not yet mechanistically understood. Here we identify interferon regulatory factor 4 (IRF4), which stimulates genes that promote immune-cell proliferation, as a key conduit for IRE1’s nonenzymatic control of cell-cycle progression in MM. IRE1 silencing increased inhibitory S114/S270 phosphorylation on IRF4, disrupting IRF4’s chromatin-binding and transcriptional activity. IRF4 knockdown recapitulated, whereas IRF4 repletion reversed, the anti-proliferative phenotype of IRE1 silencing. Furthermore, phospho-deficient, but not phospho-mimetic, IRF4 mutants rescued proliferation under IRE1 silencing. Functional studies revealed that IRF4 engages the E2F1 and CDC25A genes and promotes CDK2 activation to drive cell-cycle progression. Our results advance mechanistic understanding of IRE1 and IRF4 in MM.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ E2F1 Transcription Factor - genetics
/ E2F1 Transcription Factor - metabolism
/ Endoplasmic Reticulum Stress
/ Endoribonucleases - genetics
/ Endoribonucleases - metabolism
/ Enzymes
/ Gene Expression Regulation, Neoplastic
/ Genes
/ Genomes
/ Humans
/ Inositol
/ Interferon regulatory factor
/ Interferon regulatory factor 4
/ Interferon Regulatory Factors - genetics
/ Interferon Regulatory Factors - metabolism
/ Kinases
/ Medicine and Health Sciences
/ Multiple Myeloma - metabolism
/ Multiple Myeloma - pathology
/ Protein Serine-Threonine Kinases - genetics
/ Protein Serine-Threonine Kinases - metabolism
/ Proteins
