Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 4 October 2005
Vol. 2005, Issue 304, p. pe49
[DOI: 10.1126/stke.3042005pe49]

PERSPECTIVES

SLIM Trims STATs: Ubiquitin E3 Ligases Provide Insights for Specificity in the Regulation of Cytokine Signaling

Daniela Ungureanu1 and Olli Silvennoinen1,2*

1Institute of Medical Technology, University of Tampere, 33014, Tampere, Finland.
2Department of Clinical Microbiology, Tampere University Hospital, Tampere, Finland.

Abstract: The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway has evolved to serve highly specialized functions in the regulation of hematopoiesis, cell metabolism, and immune responses. The duration, strength, and specificity of cytokine signaling are controlled by several mechanisms, including the ubiquitin-proteasome pathway, which modulates the turnover of cytokine receptors and activated JAKs. The specificity of the ubiquitin pathway is achieved through various E3 ligase complexes that recognize and interact with distinct target proteins, often in a phosphorylation-dependent manner. Intriguing new information about the ubiquitin pathway came with the identification of an E3 ubiquitin ligase, SLIM, that specifically interacts with activated STAT1 and STAT4 and induces their ubiquitination and degradation. These findings, together with the evidence from paramyxoviruses about the role of ubiquitination as a highly specific STAT inhibition mechanism, highlight the role of E3 ubiquitin ligases as specificity determinants in the regulation of STAT activation, and open the field for investigation of additional E3s that target other STAT proteins.

*Corresponding author. Telephone, 358-3-3551-7845; fax, 358-3-3551-7332; e-mail, olli.silvennoinen{at}uta.fi

Citation: D. Ungureanu, O. Silvennoinen, SLIM Trims STATs: Ubiquitin E3 Ligases Provide Insights for Specificity in the Regulation of Cytokine Signaling. Sci. STKE 2005, pe49 (2005).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Ubiquitin-Specific Protease 13 Regulates IFN Signaling by Stabilizing STAT1.
H.-M. Yeh, C.-Y. Yu, H.-C. Yang, S.-H. Ko, C.-L. Liao, and Y.-L. Lin (2013)
J. Immunol. 191, 3328-3336
   Abstract »    Full Text »    PDF »
Dual Mechanism of Impairment of Interleukin-7 (IL-7) Responses in Human Immunodeficiency Virus Infection: Decreased IL-7 Binding and Abnormal Activation of the JAK/STAT5 Pathway.
O. Juffroy, F. Bugault, O. Lambotte, I. Landires, J.-P. Viard, L. Niel, A. Fontanet, J.-F. Delfraissy, J. Theze, and L. A. Chakrabarti (2010)
J. Virol. 84, 96-108
   Abstract »    Full Text »    PDF »
Elucidating the Secretion Proteome of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells.
S. K. Sze, D. P. V. de Kleijn, R. C. Lai, E. Khia Way Tan, H. Zhao, K. S. Yeo, T. Y. Low, Q. Lian, C. N. Lee, W. Mitchell, et al. (2007)
Mol. Cell. Proteomics 6, 1680-1689
   Abstract »    Full Text »    PDF »
Osteopontin Induces Ubiquitin-Dependent Degradation of STAT1 in RAW264.7 Murine Macrophages.
C. Gao, H. Guo, Z. Mi, M. J. Grusby, and P. C. Kuo (2007)
J. Immunol. 178, 1870-1881
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882