Monocyte chemotactic protein-induced protein-1 enhances DR5 degradation and negatively regulates DR5 activation-induced apoptosis through its deubiquitinase function
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.
You-Take Oh; Guoqing Qian; Jiusheng Deng; Shi-Yong Sun
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression'
Response to 'Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression', Published online: 25 May 2018; doi:10.1038/s41375-018-0155- ... more
Coppery inks paint an underwater rainbow
Coppery inks paint an underwater rainbow, Published online: 25 May 2018; doi:10.1038/d41586-018-05282-y
Inexpensive version of luminescent pigment shrugs off water. more
Previous studies suggested that MeCP2 competes with linker histone H1, but this hypothesis has never been tested in vivo. Here, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of Flag-tagged-H1.0 in mouse forebrain excitatory neurons. Unexpectedly, Flag-H1.0 and ... more
Olympus Microscopy has partnered with the Nature Publishing Group to present the Neurotechniques Collection. This compilation of articles will draw together some of the groundbreaking research that has recently been published in Nature Reviews Neuroscience and Nature Methods. Sponsored by O ... more