Irf8
Function
Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:12393690, PubMed:2111015). Can both act as a transcriptional activator or repressor (PubMed:2111015). Plays a negative regulatory role in cells of the immune system (PubMed:2111015). Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (PubMed:12393690, PubMed:22992524). Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (PubMed:12393690, PubMed:12461077, PubMed:12538667, PubMed:23382217). Positively regulates macroautophagy in dendritic cells (By similarity). Acts as a transcriptional repressor of osteoclast differentiation factors such as NFATC1 and EEIG1 (PubMed:32741026).
Post-translational modifications
Ubiquitinated (PubMed:17579016). Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes (PubMed:17579016). Ubiquitination leads to its degradation by the proteasome (By similarity).
Sumoylated with SUMO3. Desumoylated by SENP1.
Sequence Similarities
Belongs to the IRF family.
Tissue Specificity
Expressed in bone marrow macrophages (at protein level) (PubMed:32741026). Mainly expressed in lymphoid tissues (PubMed:2111015). Predominantly expressed in CD8(+)-expressing dendritic cells (PubMed:12393690).
Cellular localization
- Nucleus
- Cytoplasm
- In resting macrophages, localizes in the cytoplasm. Translocated in the nucleus upon IFN-gamma induction.
Alternative names
Icsbp, Icsbp1, Irf8, Interferon regulatory factor 8, IRF-8, Interferon consensus sequence-binding protein, ICSBP