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Proc Natl Acad Sci U S A. 2017 Jan 17;114(3):562-567. doi: 10.1073/pnas.1612195114. Epub 2016 Dec 28.

CD74 is a novel transcription regulator.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Hematology Institute, Kaplan Medical Center, Rehovot 76100, Israel.
3
Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Department of Hematology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
5
Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510.
6
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel; idit.shachar@weizmann.ac.il.

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.

KEYWORDS:

CD74; CLL; NF-κB; RUNX; transcription

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