Proto-oncogene PML controls genes devoted to MHC class I antigen presentation.
Zheng, Pan; Guo, Yong; Niu, Qingtian; Levy, David E.; Dyck, Jacqueline A.; Lu, Shengli; Sheiman, Lori A.; Liu, Yang
[Letter]
Nature.
396(6709):373-376, November 26, 1998.
(Format: HTML)
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 MHC [1-5], 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 lines [6,7] and spontaneous tumours [8-10], 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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