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Updated: May 27, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Dual-specific phosphatase DUSP21 is a novel negative feedback regulator for STAT3
Shota Shikata1, Kazuna Kikkawa1, Masahiro Fujimuro1
1Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan.
Abstract:
Dual-specificity phosphatases (DUSPs) catalyze the dephosphorylation of tyrosine and serine/threonine residues in target proteins. Atypical DUSPs (aDUSPs) lack substrate-binding motifs, suggesting their potential to target a diverse array of substrates. This study demonstrated that DUSP21, an aDUSP, is induced by leukemia inhibitory factor (LIF) in HeLa cells and acts as a negative regulator of LIF-induced signal transducer and activator of transcription 3 (STAT3) activation. Overexpressed DUSP21 co-localized and interacted with STAT3 in HeLa cells. Recombinant DUSP21 directly dephosphorylated STAT3 in vitro. Additionally, DUSP21 overexpression modulated STAT3-dependent growth of Ba/F3-G133 cells. These findings indicate that LIF-induced DUSP21 exerts an inhibitory effect on the LIF/STAT3 signaling pathway, thereby functioning as a suppressor of STAT3-mediated transcriptional activity.
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