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MgcRacGAP inhibition stimulates JAK‐dependent STAT3 activity
Author(s) -
van Adrichem Arjan J.,
Wennerberg Krister
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.11.013
Subject(s) - microbiology and biotechnology , stat3 , phosphorylation , gtpase , stat protein , stat1 , autocrine signalling , biology , gene silencing , guanine nucleotide exchange factor , chemistry , small interfering rna , cytokinesis , cell , biochemistry , rna , receptor , gene , cell division
Male germ cell Rac GTPase‐activating protein (MgcRacGAP) is a core regulator of cytokinesis. Furthermore, it appears to be involved in human oncogenesis through cytokinesis‐independent mechanisms and has been reported to be essential for nuclear translocation of signal transducer and activator of transcription (STAT) proteins, including the oncoprotein STAT3. Here we utilized MgcRacGAP inhibitor compound 1 (MINC1), a small molecule inhibitor of MgcRacGAP, to further investigate how MgcRacGAP regulates STAT3. Surprisingly, both MINC1 treatment and small interference RNA (siRNA)‐mediated gene silencing of MgcRacGAP resulted in increased STAT3 phosphorylation and STAT3‐driven transcriptional activity in our experimental systems. Finally, we demonstrated that MINC1‐induced STAT3 activation likely is due to increased STAT3 phosphorylation caused by a Rac1‐PAR3‐IL6‐IL6R‐JAK2 mediated autocrine/paracrine mechanism.