Keratin 17 Impacts Global Gene Expression and Controls G2/M Cell Cycle Transition in Ionizing Radiation-Induced Skin Damage

ZhiCao Yue; JianQiong Lin; XiaoPeng Lu; QingXiang Gao; MeiPing Pan; YaFei Zhang; SiTing Shen; Wei-Guo Zhu; Ralf Paus

doi:10.1016/j.jid.2023.02.043

Keratin 17 Impacts Global Gene Expression and Controls G2/M Cell Cycle Transition in Ionizing Radiation-Induced Skin Damage

J Invest Dermatol. 2023 Dec;143(12):2436-2446.e13. doi: 10.1016/j.jid.2023.02.043. Epub 2023 Jul 4.

Authors

ZhiCao Yue¹, JianQiong Lin², XiaoPeng Lu³, QingXiang Gao⁴, MeiPing Pan⁴, YaFei Zhang², SiTing Shen², Wei-Guo Zhu³, Ralf Paus⁵

Affiliations

¹ Department of Cell Biology & Medical Genetics, Shenzhen University Medical School, Shenzhen, China; International Cancer Center, Shenzhen University Medical School, Shenzhen, China; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University Medical School, Shenzhen, China. Electronic address: zyue@szu.edu.cn.
² Department of Cell Biology & Medical Genetics, Shenzhen University Medical School, Shenzhen, China; International Cancer Center, Shenzhen University Medical School, Shenzhen, China; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University Medical School, Shenzhen, China.
³ International Cancer Center, Shenzhen University Medical School, Shenzhen, China; Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Shenzhen University Medical School, Shenzhen, China; Department of Biochemistry & Molecular Biology, Shenzhen University Medical School, Shenzhen, China.
⁴ Institute of Life Sciences, Fuzhou University, Fuzhou, China.
⁵ Dr. Philip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Center for Dermatology Research, School of Biological Sciences, The University of Manchester and NIHR Biomedical Research Center, Manchester, United Kingdom.

PMID: 37414246
DOI: 10.1016/j.jid.2023.02.043

Abstract

Keratin 17 (K17) is a cytoskeletal protein that is part of the intermediate filaments in epidermal keratinocytes. In K17^-/- mice, ionizing radiation induced more severe hair follicle damage, whereas the epidermal inflammatory response was attenuated compared with that in wild-type mice. Both p53 and K17 have a major impact on global gene expression because over 70% of the differentially expressed genes in the skin of wild-type mice showed no expression change in p53^-/- or K17^-/- skin after ionizing radiation. K17 does not interfere with the dynamics of p53 activation; rather, global p53 binding in the genome is altered in K17^-/- mice. The absence of K17 leads to aberrant cell cycle progression and mitotic catastrophe in epidermal keratinocytes, which is due to nuclear retention, thus reducing the degradation of B-Myb, a key regulator of the G2/M cell cycle transition. These results expand our understanding of the role of K17 in regulating global gene expression and ionizing radiation-induced skin damage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Cycle / genetics
Gene Expression
Keratin-17*
M Cells
Mice
Radiation, Ionizing
Radiodermatitis*
Tumor Suppressor Protein p53

Substances

Keratin-17
Tumor Suppressor Protein p53
Krt17 protein, mouse