tailieunhanh - Báo cáo khóa học: Interaction between the 2¢)5¢ oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1

The human 2¢)5¢ oligoadenylate synthetases (OAS) form a conserved family of interferon-induced proteins consisting of four genes:OAS1, OAS2, OAS3and the 2¢)5¢ oligo-adenylate synthetase-like gene (OASL). When activated by double-strandedRNA,OAS1–3polymerizeATP into2¢)5¢-linkedoligoadenylates; 2¢)5¢-linkedoligoadenylates, in turn, activate a latent endoribonuclease that degrades viral and cellular RNAs. In contrast, while the p59 OASLprotein is highlyhomologous to theOAS family (45%identity), its 350 amino acid N-terminal domain lacks 2¢)5¢ oligoadenylate synthetase activity. . | Eur. J. Biochem. 271 628-636 2004 FEBS 2004 doi Interaction between the 2 -5 oligoadenylate synthetase-like protein p59 OASL and the transcriptional repressor methyl CpG-binding protein 1 Jesper B. Andersen Dorthe J. Strandbygard Rune Hartmannt and Just Justesen Department of Molecular Biology MBI University of Aarhus Denmark The human 2 -5 oligoadenylate synthetases OAS form a conserved family of interferon-induced proteins consisting of four genes OAS1 OAS2 OAS3 and the 2 -5 oligoadenylate synthetase-like gene OASL . When activated by double-stranded RNA OAS1-3 polymerize ATP into 2 -5 -linked oligoadenylates 2 -5 -linked oligoadenylates in turn activate a latent endoribonuclease that degrades viral and cellular RNAs. In contrast while the p59 OASL protein is highly homologous to the OAS family 45 identity its 350 amino acid N-terminal domain lacks 2 -5 oligoadenylate synthetase activity. A C-terminal 164 amino acid domain which is 30 homologous to a tandem repeat of ubiquitin further distinguishes the p59 OASLprotein and suggests that it serves a biological role which is distinct from other OAS family members. To dissect the function of p59 OASL we utilized the yeast two-hybrid system to identify interacting proteins. Methyl CpG-binding protein 1 MBD1 which functions as a transcriptional repressor was identified as a strong p59 OASL mteractor. hreeeestmgly lk e p59 OASL transcription of the MBD1 gene was induced by interferon indicating that these genes are co-ordinately regulated. The interaction was confirmed in vitro and in vivo and was mapped to the ubiquitin-like domain of p59 OASL. The p59 OASL-MBD1 interaction was specific because p59 OASL did not interact with any of the other MBD family members and MBD1 did not interact with OAS1. These findings link the p59 OASLwith MBD1 transcriptional control in the context of an interferon-stimulated cell and provide the basis for future studies to examine the functional role of this