STAT4 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

Abstract

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 erSTAT 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 yrSTAT 4) is confined to the chromosomal compartment. This distinct pattern of pS erSTAT 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.

Journal details

Volume 31
Issue number 10
Pages 1663-1673
Available online
Publication date