Nuclear b-arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-r (Mol Cell, 2008, 31:695-707)

報告日期: 2008/12/02
報告時間: 15:10/16:00
報告學生: 蔡政潔(英文報告)
講評老師: 蘇五洲

Nuclear b-Arrestin1 functions as a scaffold for the dephosphorylation of STAT1 and moderates the antiviral activity of IFN-g

Mo, W. et al., Mol. Cell 31: 695-707 (2008).


Student: Cheng-Chieh Tsai (蔡政潔)

Commentator: Dr. Wu-Chou Su (蘇五洲 教授)

Time: 15:10-16:00, Dec. 2, 2008

Place: Room 602



IFN-g, a type II immune IFN, promotes antiviral effect, antiproliferation and immune responses. IFN-g binding induces the Janus tyrosine kinases and signal transducer and activator of transcription (Jak/STAT) signaling to regulate IFN-g-inducible gene expression. For feedback regulation, it is now known that suppressor of cytokine signaling (SOCS) proteins interact with Jaks and inhibits its catalytic activity to suppress IFN-g signaling in cytoplasm.1 In addition to SOCS, T cell protein tyrosine phosphatase (TC45) is the primary protein tyrosine phosphatase (PTPase) can dephosphorylation of STAT1 in nucleus; however, its activation and effects are not well understood.2 b-arrestins are ubiquitous scarffold proteins, which interact with several proteins in the cytoplasm. Current studies demonstrate b-arrestin 1 can associate with specific promoter regions, recruit the histone acetyl transferase p300, and then promote gene expression3. In this paper, the authors investigated the regulatory mechanism of b-arrestin 1 on STAT1, TC45 and b-arrestin 1 signaling complex. They found that b-arrestin 1 acted as a scaffold that directly interacts with c-terminal of STAT1 and enhances STAT1 dephosphorylation at Tyr701 by recruiting the phosphatase TC45 following IFN-g stimulation. Futhermore, nuclear b-arrestin 1 negatively regulate STAT1 transcription activity induced by IFN-g. They further demonstrated that b-arrestin 1 interfered with IFN-g-mediated antiviral responses. Taken together, these results indicate that b-arrestin 1, is a scaffold for tyrosine dephosphorylation of STAT1 in nucleus as a negatively regulator of antiviral IFN-g responses.



1.         Schroder, K. et al. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75: 163-189 (2004).

2.         ten Hoeve, J. et al. Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol. Cell. Biol. 22: 5662-5668 (2002).

3.         Kang, J. et al. A nuclear function of beta-arrestin1 in GPCR signaling: regulation of histone acetylation and gene transcription. Cell 123: 833-847 (2005).