p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin

Denny L Cottle, Kai Kretzschmar, Harald P Gollnick, Sven R Quist

Research output: Contribution to journalLetterOtherpeer-review

Abstract

BACKGROUND: The role of p53 in the pathogenesis of skin diseases such as plaque-type psoriasis has long been questioned but never resolved. OBJECTIVES: In this study we set out to determine the contribution of p53 activity to defective interfollicular epidermal skin differentiation in a murine hyperproliferative skin model. METHODS: We used the tamoxifen-inducible K14MycER mouse model which exhibits abnormal epidermal differentiation in response to high MYC activity, crossed with p53 knock-out mice. Results- We show that genetic deletion of p53 leads to improvements in granular layer formation. Furthermore, we show that p53 activity regulates down-stream expression of Keratin 6a, Pparb/d and Pparg and is regulated upstream by retinoic acid signalling-dependent mechanisms. CONCLUSION: We conclude aberrant non-apoptotic p53 activity contributes, in-part, to abnormal differentiation and granular layer defects. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)204-208
Number of pages5
JournalBritish Journal of Dermatology
Volume174
Issue number1
DOIs
Publication statusPublished - 2016

Cite this

@article{7e3e995efe96440d9cba5234128272cf,
title = "p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin",
abstract = "BACKGROUND: The role of p53 in the pathogenesis of skin diseases such as plaque-type psoriasis has long been questioned but never resolved. OBJECTIVES: In this study we set out to determine the contribution of p53 activity to defective interfollicular epidermal skin differentiation in a murine hyperproliferative skin model. METHODS: We used the tamoxifen-inducible K14MycER mouse model which exhibits abnormal epidermal differentiation in response to high MYC activity, crossed with p53 knock-out mice. Results- We show that genetic deletion of p53 leads to improvements in granular layer formation. Furthermore, we show that p53 activity regulates down-stream expression of Keratin 6a, Pparb/d and Pparg and is regulated upstream by retinoic acid signalling-dependent mechanisms. CONCLUSION: We conclude aberrant non-apoptotic p53 activity contributes, in-part, to abnormal differentiation and granular layer defects. This article is protected by copyright. All rights reserved.",
author = "Cottle, {Denny L} and Kai Kretzschmar and Gollnick, {Harald P} and Quist, {Sven R}",
year = "2016",
doi = "10.1111/bjd.14048",
language = "English",
volume = "174",
pages = "204--208",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley-Blackwell",
number = "1",

}

p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin. / Cottle, Denny L; Kretzschmar, Kai; Gollnick, Harald P; Quist, Sven R.

In: British Journal of Dermatology, Vol. 174, No. 1, 2016, p. 204-208.

Research output: Contribution to journalLetterOtherpeer-review

TY - JOUR

T1 - p53 activity contributes to defective interfollicular epidermal differentiation, in hyperproliferative murine skin

AU - Cottle, Denny L

AU - Kretzschmar, Kai

AU - Gollnick, Harald P

AU - Quist, Sven R

PY - 2016

Y1 - 2016

N2 - BACKGROUND: The role of p53 in the pathogenesis of skin diseases such as plaque-type psoriasis has long been questioned but never resolved. OBJECTIVES: In this study we set out to determine the contribution of p53 activity to defective interfollicular epidermal skin differentiation in a murine hyperproliferative skin model. METHODS: We used the tamoxifen-inducible K14MycER mouse model which exhibits abnormal epidermal differentiation in response to high MYC activity, crossed with p53 knock-out mice. Results- We show that genetic deletion of p53 leads to improvements in granular layer formation. Furthermore, we show that p53 activity regulates down-stream expression of Keratin 6a, Pparb/d and Pparg and is regulated upstream by retinoic acid signalling-dependent mechanisms. CONCLUSION: We conclude aberrant non-apoptotic p53 activity contributes, in-part, to abnormal differentiation and granular layer defects. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: The role of p53 in the pathogenesis of skin diseases such as plaque-type psoriasis has long been questioned but never resolved. OBJECTIVES: In this study we set out to determine the contribution of p53 activity to defective interfollicular epidermal skin differentiation in a murine hyperproliferative skin model. METHODS: We used the tamoxifen-inducible K14MycER mouse model which exhibits abnormal epidermal differentiation in response to high MYC activity, crossed with p53 knock-out mice. Results- We show that genetic deletion of p53 leads to improvements in granular layer formation. Furthermore, we show that p53 activity regulates down-stream expression of Keratin 6a, Pparb/d and Pparg and is regulated upstream by retinoic acid signalling-dependent mechanisms. CONCLUSION: We conclude aberrant non-apoptotic p53 activity contributes, in-part, to abnormal differentiation and granular layer defects. This article is protected by copyright. All rights reserved.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26212071

U2 - 10.1111/bjd.14048

DO - 10.1111/bjd.14048

M3 - Letter

VL - 174

SP - 204

EP - 208

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 1

ER -