Editors' ChoiceImmunology

Tumor suppressor p53 linked to immune function

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Sci. Signal.  04 Aug 2015:
Vol. 8, Issue 388, pp. ec220
DOI: 10.1126/scisignal.aad1352

In conditions of cell stress, the activity of the tumor suppressor p53 can lead to cell death by apoptosis. One of the genes that p53 induces encodes DD1 α, a receptor-like transmembrane protein of the immunoglobulin superfamily. Yoon et al. describe a previously unrecognized function of the tumor suppressor p53 (see the Perspective by Zitvogel and Kroemer). By inducing an increase in DD1 α, p53 also promoted the clearance of dead cells through engulfment by macrophages. Furthermore, analysis of DD1 α-deficient mice indicated that on T cells DD1 α functions as a negative regulator of T cells. Thus, p53 offers protection from inflammatory disease caused by the accumulation of apoptotic cells, and, by suppressing T cells, p53 might help cancer cells to escape immune detection.

K. W. Yoon, S. Byun, E. Kwon, S.-Y. Hwang, K. Chu, M. Hiraki, S.-H. Jo, A. Weins, S. Hakroush, A. Cebulla, D. B. Sykes, A. Greka, P. Mundel, D. E. Fisher, A. Mandinova, S. W. Lee, Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science 349, 1261669 (2015). [Abstract] [Full Text]

L. Zitvogel, G. Kroemer, A p53-regulated immune checkpoint relevant to cancer. Science 349, 476-477 (2015). [Abstract] [Full Text]