Unknown,Transcriptomics,Genomics,Proteomics

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Effect of LMP7 and MECL1-immunoproteasome subunits deficiency on the transcriptome of mouse bone marrow-derived dendritic cells


ABSTRACT: As regulators of protein degradation, proteasomes regulate practically all cellular functions. It is therefore logical to assume that replacement of the constitutive proteasome (CP) by its IFN- inducible homolog immunoproteasome (IP) could have far reaching effects on cell function. Accordingly, recent studies have revealed important roles for IPs in immune cells beyond MHC I-peptide processing. Moreover, the expression of IPs in non-immune cells from non-inflamed tissues suggests that the involvement of IPs is not limited to the immune system. We demonstrate here that IP-deficiency affects the transcription of 8104 genes in maturing dendritic cells (DCs). This occurs mainly through non-redundant regulation of key immune-related transcription factors by CPs and IPs. Additionally, IP-deficiency decreases DC's efficiency to activate CD8+ T cells in vivo. Our study reveals that the broad cellular roles of IPs could rely on transcription regulation and, more importantly, illustrates how IP-deficiency could generate MHC I-peptide processing-independent phenotypes. Examination of the transcriptome of WT and immunoproteasome-deficient cells at 4 different time points of dendritic cell maturation, in 4 experimental replicates (total of 32 samples).

ORGANISM(S): Mus musculus

SUBMITTER: Claude Perreault 

PROVIDER: E-GEOD-52616 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Immunoproteasomes shape the transcriptome and regulate the function of dendritic cells.

de Verteuil Danielle A DA   Rouette Alexandre A   Hardy Marie-Pierre MP   Lavallée Stéphanie S   Trofimov Assya A   Gaucher Étienne É   Perreault Claude C  

Journal of immunology (Baltimore, Md. : 1950) 20140623 3


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 regul  ...[more]

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