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. 2018 Jun;37(25):3415-3425.
doi: 10.1038/s41388-018-0200-9. Epub 2018 Mar 19.

Monocyte chemotactic protein-induced protein-1 enhances DR5 degradation and negatively regulates DR5 activation-induced apoptosis through its deubiquitinase function

You-Take Oh  1 , Guoqing Qian  1 , Jiusheng Deng  1 , Shi-Yong Sun  2
Affiliations

Monocyte chemotactic protein-induced protein-1 enhances DR5 degradation and negatively regulates DR5 activation-induced apoptosis through its deubiquitinase function

You-Take Oh et al. Oncogene. 2018 Jun.

Abstract

Monocyte chemotactic protein-induced protein-1 (MCPIP1; also called Regnase-1) encoded by the ZC3H12A gene critically regulates inflammatory responses and immune homeostasis primarily by RNase-dependent and -independent mechanisms. However, the relationship of MCPIP1 with apoptosis and cancer and the underlying mechanisms are largely unclear. The current study has demonstrated a previously uncovered connection between MCPIP1 and the negative regulation of death receptor 5 (DR5; also known as TRAIL-R2 or killer/DR5), a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is produced endogenously by various immune cells such as T cells. Our findings have revealed that MCPIP1 decreases both total cellular and cell surface DR5, primarily through modulating DUB-mediated protein autophagic/lysosomal degradation. Suppression of MCPIP1 by gene knockdown induces the formation of death-induced signaling complex (DISC) and enhances TRAIL or DR5 activation-induced apoptosis in cancer cells. Moreover, we demonstrated an inverse correlation between MCPIP1 expression and DR5 expression/cell sensitivity to DR5 activation-induced apoptosis in cancer cells. Our findings warrant future investigation of the roles of negative regulation of DR5 by MCPIP1 in cancer and in T-cell immunity.

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References

    1. Autophagy. 2016 Dec;12 (12 ):2451-2466 - PubMed
    1. Gastroenterology. 2009 Jun;136(7):2365-2376.e1-7 - PubMed
    1. Immunology. 2009 Jun;127(2):145-54 - PubMed
    1. Cancer Biol Ther. 2009 May;8(10):917-22 - PubMed
    1. Mol Cancer. 2010 Dec 20;9:315 - PubMed

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