Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada; and Department of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada.
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec H3C 3J7, Canada; and.
J Immunol. 2014 Aug 1;193(3):1121-32. doi: 10.4049/jimmunol.1400871. Epub 2014 Jun 23.
By regulating protein degradation, constitutive proteasomes (CPs) control practically all cellular functions. In addition to CPs, vertebrates express immunoproteasomes (IPs). The major nonredundant role ascribed to IPs is their enhanced ability to generate antigenic peptides. We report that CPs and IPs differentially regulate the expression of >8000 transcripts in maturing mouse dendritic cells (DCs) via regulation of signaling pathways such as IFN regulatory factors, STATs, and NF-κB. IPs regulate the transcription of many mRNAs and maturation of a few of them. Moreover, even when engineered to present optimal amounts of antigenic peptide, IP-deficient DCs are inefficient for in vivo T cell priming. Our study shows that the role of IPs in DCs is not limited to Ag processing and reveals a major nonredundant role for IPs in transcription regulation. The dramatic effect of IPs on the transcriptional landscape could explain the various immune and nonimmune phenotypes observed in vertebrates with IP deficiency or mutations.
通过调节蛋白质降解，组成型蛋白酶体（CPs）控制着几乎所有的细胞功能。除了 CPs，脊椎动物还表达免疫蛋白酶体（IPs）。IPs 的主要非冗余作用是增强其产生抗原肽的能力。我们报告称，CPs 和 IPs 通过调节 IFN 调节因子、STAT 和 NF-κB 等信号通路，差异调节成熟的小鼠树突状细胞（DCs）中 >8000 个转录本的表达。IPs 调节许多 mRNA 的转录和其中一些的成熟。此外，即使工程化以呈现最佳量的抗原肽，IP 缺陷型 DCs 在体内 T 细胞启动中效率低下。我们的研究表明，IPs 在 DCs 中的作用不仅限于 Ag 加工，并揭示了 IPs 在转录调控中的主要非冗余作用。IPs 对转录景观的巨大影响可以解释在具有 IP 缺陷或突变的脊椎动物中观察到的各种免疫和非免疫表型。
