| First Author | Kroczynska B | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 31 | Pages | 11377-82 |
| PubMed ID | 25049393 | Mgi Jnum | J:212231 |
| Mgi Id | MGI:5578375 | Doi | 10.1073/pnas.1405250111 |
| Citation | Kroczynska B, et al. (2014) Regulatory effects of SKAR in interferon alpha signaling and its role in the generation of type I IFN responses. Proc Natl Acad Sci U S A 111(31):11377-82 |
| abstractText | We provide evidence that S6 kinase 1 (S6K1) Aly/REF-like target (SKAR) is engaged in IFN-alpha signaling and plays a key role in the generation of IFN responses. Our data demonstrate that IFN-alpha induces phosphorylation of SKAR, which is mediated by either the p90 ribosomal protein S6 kinase (RSK) or p70 S6 kinase (S6K1), in a cell type-specific manner. This type I IFN-inducible phosphorylation of SKAR results in enhanced interaction with the eukaryotic initiation factor (eIF)4G and recruitment of activated RSK1 to 5' cap mRNA. Our studies also establish that SKAR is present in cap-binding CBP80 immune complexes and that this interaction is mediated by eIF4G. We demonstrate that inducible protein expression of key IFN-alpha-regulated protein products such as ISG15 and p21(WAF1/CIP1) requires SKAR activity. Importantly, our studies define a requirement for SKAR in the generation of IFN-alpha-dependent inhibitory effects on malignant hematopoietic progenitors from patients with chronic myeloid leukemia or myeloproliferative neoplasms. Taken altogether, these findings establish critical and essential roles for SKAR in the regulation of mRNA translation of IFN-sensitive genes and induction of IFN-alpha biological responses. |
