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STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin and mucosa derived cell type: implications in neoplastic and inflammatory skin diseases

STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin and mucosa derived cell type: implications in neoplastic and inflammatory skin diseases
STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin and mucosa derived cell type: implications in neoplastic and inflammatory skin diseases
Background
The signal transducer and activator of transcription-4 (STAT4/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 STAT4 in cell mitosis.

Results
Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis, and is distributed throughout the cytoplasm during this stage of the cell cycle whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 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 STAT4 phosphorylation by lisofylline and depletion of STAT4 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 STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.
0926-9959
1663-1673
Ferreli, C.
653fd760-6115-4da6-8c6e-bde91c00da64
Lai, C.
29ba48ea-2d38-497f-8cf9-400237f6a3a0
August, S.
e17f5022-087a-4ca2-9345-364356b37d58
Buggy, Y.
b3ad4b24-fde8-47c1-a728-96e4b9df6b3b
Kumar, P.
f57e4ef2-18e6-4f90-be71-7450c42df258
Brownlow, N.
ea89657d-2a2c-43d0-bb66-faf38086c9f7
Parker, P.
b7f36f18-00b6-4599-bc25-713b6ee102f0
Friedmann, P.S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Ardern-Jones, M.
7ac43c24-94ab-4d19-ba69-afaa546bec90
Pickard, C.
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Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd
Ferreli, C.
653fd760-6115-4da6-8c6e-bde91c00da64
Lai, C.
29ba48ea-2d38-497f-8cf9-400237f6a3a0
August, S.
e17f5022-087a-4ca2-9345-364356b37d58
Buggy, Y.
b3ad4b24-fde8-47c1-a728-96e4b9df6b3b
Kumar, P.
f57e4ef2-18e6-4f90-be71-7450c42df258
Brownlow, N.
ea89657d-2a2c-43d0-bb66-faf38086c9f7
Parker, P.
b7f36f18-00b6-4599-bc25-713b6ee102f0
Friedmann, P.S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Ardern-Jones, M.
7ac43c24-94ab-4d19-ba69-afaa546bec90
Pickard, C.
4d8b8c85-8118-4a54-b737-360344ab6e40
Healy, E.
400fc04d-f81a-474a-ae25-7ff894be0ebd

Ferreli, C., Lai, C., August, S., Buggy, Y., Kumar, P., Brownlow, N., Parker, P., Friedmann, P.S., Ardern-Jones, M., Pickard, C. and Healy, E. (2017) STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin and mucosa derived cell type: implications in neoplastic and inflammatory skin diseases. Journal of the European Academy of Dermatology and Venereology, 31 (10), 1663-1673. (doi:10.1111/jdv.14342).

Record type: Article

Abstract

Background
The signal transducer and activator of transcription-4 (STAT4/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 STAT4 in cell mitosis.

Results
Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis, and is distributed throughout the cytoplasm during this stage of the cell cycle whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 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 STAT4 phosphorylation by lisofylline and depletion of STAT4 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 STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

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STAT4_JEADV_2017_final_accepted_manuscript - Accepted Manuscript
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Accepted/In Press date: 19 April 2017
e-pub ahead of print date: 10 August 2017
Published date: October 2017
Additional Information: Manuscript accepted 19th April 2017 (as per email message file added with manuscript and figures)
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 408073
URI: https://eprints.soton.ac.uk/id/eprint/408073
ISSN: 0926-9959
PURE UUID: e00ea2e7-b37b-4d59-9ec6-3f806d361946

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Date deposited: 11 May 2017 01:03
Last modified: 20 Jul 2019 05:09

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