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STAT 4 expression and activation is increased during mitosis in vitro and in vivo in skin‐ and mucosa‐derived cell types: implications in neoplastic and inflammatory skin diseases
Author(s) -
Ferreli C.,
Lai C.,
August S.,
Buggy Y.,
Kumar P.,
Brownlow N.,
Parker P.,
Friedmann P.S.,
ArdernJones M.,
Pickard C.,
Healy E.
Publication year - 2017
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.14342
Subject(s) - mitosis , microbiology and biotechnology , stat4 , stat , stat protein , cytokinesis , biology , cell , chemistry , cell division , stat3 , signal transduction , biochemistry
Background The signal transducer and activator of transcription‐4 ( STAT 4/Stat4) is a transcription factor known to convey signals from interleukin‐12, interleukin‐23, and interferon‐alpha/beta to the nucleus, resulting in activation of dendritic cells, T‐helper cell differentiation and production of interferon‐gamma. Objective To demonstrate a novel role for STAT 4 in cell mitosis. Results Phosphoserine STAT 4 ( pS er STAT 4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT 4 ( pT yr STAT 4) is confined to the chromosomal compartment. This distinct pattern of pS er STAT 4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT 4 phosphorylation by lisofylline and depletion of STAT 4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. Conclusion Our data demonstrate that STAT 4 plays a role in enabling the normal and timely division of cells undergoing mitosis.