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Proto-oncogene PML controls genes devoted to MHC class I antigen presentation

Nature volume 396, pages 373–376 (1998)Cite this article

Abstract

Fragments of foreign antigens associated with class I molecules of the major histocompatibility complex (MHC) are presented at the cell surface to elicit an immune response. This presentation requires the coordinated expression of several genes contained in the MHC1,2,3,4,5, including those encoding the MHC class I heavy chain, the proteins LMP-2 and LMP-7, which are involved in the proteasomal degradation of cytosolic antigens into peptide fragments that are destined for association with MHC class I molecules, and TAP-1 and TAP-2, which transport these fragments across the membrane of the endoplasmic reticulum at the start of their journey to the cell surface. In many virus-transformed cell lines6,7 and spontaneous tumours8,9,10, these genes are simultaneously repressed. However, the key factor(s) that are essential for their expression and repression have not been identified. Here we report that the proto-oncogene product PML induces expression of LMP-2, LMP-7, TAP-1 and TAP-2 in an MHC-class I-negative, recurrent tumour, leading to the re-expression of cell-surface MHC in tumours and to rejection of the tumours. PML also regulates MHC expression in untransformed fibroblasts. We conclude that malfunction of PML may enable a tumour to evade the immune defence of its host.

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Figure 1: Multiple antigen-presentation defects in a recurring tumour cell line, ReB7.
Figure 2: Identification by expression cloning of a cDNA that compensates for the antigen-presentation defects of the ReB7 cell line.
Figure 3: Identification of F12 cDNA as a normal isoform of the PML gene and of a dominant-negative mutation of PML in ReB7.
Figure 4: Expression and function of PML-F12 isoform in normal murine cells.

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Acknowledgements

We thank V. Nussenzweig, X.-H. Sun and X. D. Fu for discussions and for critically reading the manuscript; J. Hirst for flow cytometry; B. Mach for the EBO-Sfi vector; S. Vukmanovic for the Kd cDNA clone; M. Lanotte for NB4 cells; and F. Hitchcock for help with preparing the manuscript. This study was supported by grants from the NIH and by the Kaplan Comprehensive Center of NYU Medical Center and by Ohio State University Comprehensive Cancer Center.

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  1. Pan Zheng & Yang Liu

    Present address: Department of Pathology, Ohio State University Medical Center, Columbus, Ohio, 43210, USA

  2. Yang Liu: Correspondence and requests for materials should be addressed to Y.L.

Authors and Affiliations

  1. Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, 10016, New York, USA

    Yong Guo, Qingtian Niu, David E. Levy, Shengli Lu & Lori A. Sheiman

  2. Department of Medicine, University of California at San Diego, La Jolla, 92093, California, USA

    Jacqueline A. Dyck

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Correspondence to Yang Liu.

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Zheng, P., Guo, Y., Niu, Q. et al. Proto-oncogene PML controls genes devoted to MHC class I antigen presentation. Nature 396, 373–376 (1998). https://doi.org/10.1038/24628

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