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Identification of murine and human XCP1 genes as C/EBP-ε-dependent members of FIZZ/Resistin gene family

Oncogene volume 23, pages 3414–3425 (2004)Cite this article

Abstract

The CCAAT enhancer binding protein epsilon (C/EBP-ɛ) transcription factor is expressed predominantly in granulocytes. Mice with a disruption of the C/EBP-ɛ gene fail to produce mature granulocytes and eosinophils. Cells derived from the peritoneal exudates of C/EBP-ɛ −/− mice lack the expression of a number of chemokines and chemokine receptor genes. We have found a novel C/EBP-ɛ-dependent promyelocyte-specific gene, mXCP1. mXCP1 belongs to a family of XCP/FIZZ/Resistin genes, which includes four murine genes and two human genes, hXCP1 and hXCP2. These genes have four exons and encode short secreted proteins sharing a ten-cysteine motif. Murine mXCP1, mXCP2 and mXCP3 genes map to murine chromosome 16 and mXCP4 is positioned on chromosome 8; the hXCP1 and hXCP2 genes are located at homologous regions of chromosomes 3 and 19. Introduction of an inducible C/EBP-ɛ gene into the NIH3T3 and myeloid cells from C/EBP-ɛ-null mice line revealed that the conditional expression of C/EBP-ɛ induced mXCP1. The HXCP1 gene was identified as a C/EBP-ɛ-dependent regulatory homologue of mXCP1. The expression data for other members of XCP/FIZZ gene family are presented. Further studies indicate that XCP1 is a secreted protein that is chemotactic to myeloid cells from C/EBP-ɛ-null mice and is able to interact directly with α-defensin.

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Acknowledgements

We are grateful to all investigators who shared their valuable reagents with us. We especially thank Drs James O'Kelly and Steffen W Nichols for their invaluable help in colony formation and antimicrobial activity assays, and Kimberly Burgin for excellent secretarial assistance. We are grateful to Drs A Gombart and Carl W Miller for helpful discussions, and Dr Doris Chih and other members of the Koeffler lab for generously sharing their reagents.

This work was supported in part by NIH grants and the Parker Hughes Fund. HPK is the holder of the Mark Goodson Chair of Oncology Research at Cedars Sinai Medical Center and is a member of the Jonsson Cancer Center and the Molecular Biology Institute (UCLA).

Sequence data for all XCP genes were deposited in GenBank under accession numbers BE847000, AF512014, AF510098, AF510099, AF510100, AF352730 and AF352731.

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  1. Division of Hematology/Oncology, Cedars-Sinai Medical Center, Burns & Allen Research Institute, UCLA School of Medicine, Los Angeles, CA, USA

    Alexey M Chumakov, Steffen Walter & H Phillip Koeffler

  2. Department of Medicine, Kochi Medical School, Kochi, Japan

    Tetsuya Kubota

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  1. Alexey M Chumakov
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Correspondence to Alexey M Chumakov.

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Chumakov, A., Kubota, T., Walter, S. et al. Identification of murine and human XCP1 genes as C/EBP-ε-dependent members of FIZZ/Resistin gene family. Oncogene 23, 3414–3425 (2004). https://doi.org/10.1038/sj.onc.1207126

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