The STAT3 isoforms α and β have unique and specific functions

Speaker: 吳育欣                           Time: 13:00-14:00 May 5, 2004

Commentator: 林秋烽博士                   Place: Room 601

Abstract:

     Signal transducer and activator of transcription 3 (STAT3) is the main mediators of IL-6-type cytokine signaling. One of the peculiar characteristics of STAT3 is its capability to activate different sets of genes in different cell types. Sometimes STAT3 revealed apparently contrasting actions such as inducing inflammatory gene expression in liver and mediating the anti-inflammatory functions of IL-10 in macrophages. What contributes to these phenomena is unclear. STAT3 exists in two isoforms: the full-length STAT3α and the truncated STAT3β, generally thought to act as a dominant negative factor. To assess their relative functions, the authors ablated the expression of either isoform by gene targeting. They show that STAT3α is required for postnatal function(s) whereas STAT3β is not required for viability. Expression of STAT3β can rescue the embryonic lethality of a STAT3-null mutation and STAT3β can by itself induce the expression of specific STAT3 target genes. These data indicate that STAT3β is not a dominant negative factor. The function of the two STAT3 isoforems in inflammation seems to be complex. In the study, STAT3 mediated IL-10 anti-inflammatory effect is by STAT3α isoform. However, STAT3β also has an anti-inflammatory function, as STAT3β-null mice are hyper-reactive to LPS and have upregulated expression of many inflammation-related genes. In addition, STAT3β may also be the isoform which contributes to the LPS-mediated induction of IL-10. The distinct properties of the two isoforms demonstrated by this study may provide the molecular basis to explain the functional heterogeneity of STAT3.

References

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2.      Alonzi, T. et al. Essential role of the signal transducer and activator of transcription STAT3 in the control of the acute-phase response as revealed by inducible gene activation in the liver. Mol. Cell. Biol. 21, 1621-1632 (2001)

3.      Yoo, J. Y. et al. Specific ablation of STAT3β distorts the pattern of STAT3-responsive gene expression and impairs the recovery from endotoxic shock. Cell 108, 331-344 (2002)