title: CD74 is a novel transcription regulator.
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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Gil-Yarom
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lihi
authors.initials: L
authors.lastname: Radomir
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Sever
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Matthias P
authors.identifier: 0000-0002-0289-5261
authors.initials: MP
authors.lastname: Kramer
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Lewinsky
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Chamutal
authors.initials: C
authors.lastname: Bornstein
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Blecher-Gonen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Barnett-Itzhaki
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Vita
authors.initials: V
authors.lastname: Mirkin
authors.affiliation: Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Gilgi
authors.initials: G
authors.lastname: Friedlander
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Lev
authors.initials: L
authors.lastname: Shvidel
authors.affiliation: Department of Hematology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Herishanu
authors.affiliation: Department of Pharmacology, Yale School of Medicine, New Haven, CT 06510.
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Lolis
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shirly
authors.initials: S
authors.lastname: Becker-Herman
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel; idit.shachar@weizmann.ac.il.
authors.forename: Idit
authors.initials: I
authors.lastname: Shachar
keywords: CD74; CLL; NF-κB; RUNX; transcription