Identification of a nuclear localization signal in suppressor of cytokine signaling 1

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Andrea BaetzAlexander H Dalpke

Abstract

Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of janus kinase and signal transducer and activators of transcription signaling pathways. In addition, SOCS1 has been identified to regulate stability of nuclear NF-kappaB subunits. However, details about the regulation of the nuclear pool of SOCS1 are unknown. Using different experimental approaches, we observed that SOCS1 but no further SOCS family members localized to the nucleus when expressed in various cell lines. Nuclear transport was confirmed for endogenous SOCS1 in macrophages stimulated with IFN-gamma. Sequence analysis revealed a bipartite nuclear localization signal (NLS) located between the src-homology 2 (SH2) domain and the SOCS box of SOCS1. Deletion of this region, introduction of a series of R/A point mutations, or substitution of this sequence with the respective region of SOCS3 resulted in loss of nuclear localization. Fusion of the SOCS1-NLS to cytokine-inducible SH2 region containing protein (CIS) resulted in nuclear localization of this otherwise cytoplasmic protein. SOCS1 mutants with loss of nuclear localization were still effective in suppressing IFN-alpha-mediated STAT1 tyrosine phosphorylation. However, they showed de...Continue Reading

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