The STAT3 isoforms α and β have unique and specific functions

Diego Maritano; Michelle L. Sugrue; Silvia Tininini; Sarah Dewilde; Birgit Strobl; XinPing Fu; Victoria Murray-Tait; Roberto Chiarle; Valeria Poli

doi:10.1038/ni1052

The STAT3 isoforms α and β have unique and specific functions

Diego Maritano
, Michelle L. Sugrue
, Silvia Tininini
, Sarah Dewilde
, Birgit Strobl
, XinPing Fu
, Victoria Murray-Tait
, Roberto Chiarle
, Valeria Poli

Research output: Contribution to journal › Article › peer-review

207 Citations (Scopus)

Abstract

Signal transducer and activator of transcription 3 (STAT3) is the main mediator of interleukin 6 (IL-6)-type cytokine signaling. It exists in two isoforms: the full-length STAT3 and the truncated STAT3, generally thought to act as a dominant negative factor. To assess their relative functions, we ablated the expression of either isoform by gene targeting. We show here that in vivo STAT3 is not a dominant negative factor. Its expression can rescue the embryonic lethality of a STAT3-null mutation and it can by itself induce the expression of specific STAT3 target genes. Nevertheless, STAT3 has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.

Original language	English
Pages (from-to)	401-409
Number of pages	9
Journal	Nature Immunology
Volume	5
Issue number	4
DOIs	https://doi.org/10.1038/ni1052
Publication status	Published - Apr 2004

Keywords

IL-10 GENE
GENE-EXPRESSION
TRANSCRIPTION FACTOR
NEGATIVE REGULATOR
STAT3-DEFICIENT MICE
ACUTE-PHASE RESPONSE
SIGNAL TRANSDUCER
C-JUN
CHRONIC ENTEROCOLITIS
IN-VIVO

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title = "The STAT3 isoforms α and β have unique and specific functions",

abstract = "Signal transducer and activator of transcription 3 (STAT3) is the main mediator of interleukin 6 (IL-6)-type cytokine signaling. It exists in two isoforms: the full-length STAT3 and the truncated STAT3, generally thought to act as a dominant negative factor. To assess their relative functions, we ablated the expression of either isoform by gene targeting. We show here that in vivo STAT3 is not a dominant negative factor. Its expression can rescue the embryonic lethality of a STAT3-null mutation and it can by itself induce the expression of specific STAT3 target genes. Nevertheless, STAT3 has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.",

keywords = "IL-10 GENE, GENE-EXPRESSION, TRANSCRIPTION FACTOR, NEGATIVE REGULATOR, STAT3-DEFICIENT MICE, ACUTE-PHASE RESPONSE, SIGNAL TRANSDUCER, C-JUN, CHRONIC ENTEROCOLITIS, IN-VIVO",

author = "Diego Maritano and Sugrue, \{Michelle L.\} and Silvia Tininini and Sarah Dewilde and Birgit Strobl and XinPing Fu and Victoria Murray-Tait and Roberto Chiarle and Valeria Poli",

year = "2004",

month = apr,

doi = "10.1038/ni1052",

language = "English",

volume = "5",

pages = "401--409",

journal = "Nature Immunology",

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TY - JOUR

T1 - The STAT3 isoforms α and β have unique and specific functions

AU - Maritano, Diego

AU - Sugrue, Michelle L.

AU - Tininini, Silvia

AU - Dewilde, Sarah

AU - Strobl, Birgit

AU - Fu, XinPing

AU - Murray-Tait, Victoria

AU - Chiarle, Roberto

AU - Poli, Valeria

PY - 2004/4

Y1 - 2004/4

N2 - Signal transducer and activator of transcription 3 (STAT3) is the main mediator of interleukin 6 (IL-6)-type cytokine signaling. It exists in two isoforms: the full-length STAT3 and the truncated STAT3, generally thought to act as a dominant negative factor. To assess their relative functions, we ablated the expression of either isoform by gene targeting. We show here that in vivo STAT3 is not a dominant negative factor. Its expression can rescue the embryonic lethality of a STAT3-null mutation and it can by itself induce the expression of specific STAT3 target genes. Nevertheless, STAT3 has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.

AB - Signal transducer and activator of transcription 3 (STAT3) is the main mediator of interleukin 6 (IL-6)-type cytokine signaling. It exists in two isoforms: the full-length STAT3 and the truncated STAT3, generally thought to act as a dominant negative factor. To assess their relative functions, we ablated the expression of either isoform by gene targeting. We show here that in vivo STAT3 is not a dominant negative factor. Its expression can rescue the embryonic lethality of a STAT3-null mutation and it can by itself induce the expression of specific STAT3 target genes. Nevertheless, STAT3 has nonredundant roles such as modulation of cellular responses to IL-6 and mediation of IL-10 function in macrophages.

KW - IL-10 GENE

KW - GENE-EXPRESSION

KW - TRANSCRIPTION FACTOR

KW - NEGATIVE REGULATOR

KW - STAT3-DEFICIENT MICE

KW - ACUTE-PHASE RESPONSE

KW - SIGNAL TRANSDUCER

KW - C-JUN

KW - CHRONIC ENTEROCOLITIS

KW - IN-VIVO

U2 - 10.1038/ni1052

DO - 10.1038/ni1052

M3 - Article

C2 - 15021879

SN - 1529-2908

VL - 5

SP - 401

EP - 409

JO - Nature Immunology

JF - Nature Immunology

IS - 4

ER -

The STAT3 isoforms α and β have unique and specific functions

Abstract

Keywords

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