CD74 is a novel transcription regulator

Naama Gil-Yarom, Lihi Radomir, Lital Sever, Matthias P. Kramer, Hadas Lewinsky, Chamutal Bornstein, Ronnie Blecher-Gonen, Zohar Barnett-Itzhaki, Vita Mirkin, Gilgi Friedlander, Lev Shvidel, Yair Herishanu, Elias J. Lolis, Shirly Becker-Herman, Ido Amit, Idit Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor. Macrophage migration inhibitory factor binding to CD74 induces its intramembrane cleavage and the release of its cytosolic intracellular domain (CD74-ICD), which regulates cell survival. In the present study, we characterized the transcriptional activity of CD74-ICD in chronic lymphocytic B cells. We show that following CD74 activation, CD74-ICD interacts with the transcription factors RUNX (Runt related transcription factor) and NF-κB and binds to proximal and distal regulatory sites enriched for genes involved in apoptosis, immune response, and cell migration. This process leads to regulation of expression of these genes. Our results suggest that identifying targets of CD74 will help in understanding of essential pathways regulating B-cell survival in health and disease.

Original languageAmerican English
Pages (from-to)562-567
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number3
DOIs
StatePublished - 17 Jan 2017
Externally publishedYes

Keywords

  • CD74
  • CLL
  • NF-κB
  • RUNX
  • Transcription

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