Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis
文献类型：期刊论文
| 作者 | Lee, Philbert1; Jiang, Shangwen2,3; Li, Yuanyuan1; Yue, Jiping1; Gou, Xuewen1; Chen, Shao-Yu4; Zhao, Yingming1 ; Schober, Markus5; Tan, Minjia2,3; Wu, Xiaoyang1
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| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2017-07-03 |
| 卷号 | 36期号:13页码:1963-1980 |
| 关键词 | differentiation epidermal progenitor cell skin tumorigenesis |
| ISSN号 | 0261-4189 |
| DOI | 10.15252/embj.201695679 |
| 文献子类 | Article |
| 英文摘要 | Tissue homeostasis of skin is sustained by epidermal progenitor cells localized within the basal layer of the skin epithelium. Posttranslational modification of the proteome, such as protein phosphorylation, plays a fundamental role in the regulation of stemness and differentiation of somatic stem cells. However, it remains unclear how phosphoproteomic changes occur and contribute to epidermal differentiation. In this study, we survey the epidermal cell differentiation in a systematic manner by combining quantitative phosphoproteomics with mammalian kinome cDNA library screen. This approach identified a key signaling event, phosphorylation of a desmosome component, PKP1 (plakophilin-1) by RIPK4 (receptor-interacting serine-threonine kinase 4) during epidermal differentiation. With genome-editing and mouse genetics approach, we show that loss of function of either Pkp1 or Ripk4 impairs skin differentiation and enhances epidermal carcinogenesis in vivo. Phosphorylation of PKP1's N-terminal domain by RIPK4 is essential for their role in epidermal differentiation. Taken together, our study presents a global view of phosphoproteomic changes that occur during epidermal differentiation, and identifies RIPK-PKP1 signaling as novel axis involved in skin stratification and tumorigenesis. |
| WOS关键词 | SQUAMOUS-CELL CARCINOMA ; FOCAL ADHESION DYNAMICS ; PROTEIN-KINASE ; STEM-CELLS ; IN-VIVO ; KERATINOCYTE DIFFERENTIATION ; QUANTITATIVE-PROTEOMICS ; FRAGILITY-SYNDROME ; TGF-BETA ; DESMOSOME |
| 资助项目 | National Institutes of Health[R01-AR063630] ; National Institutes of Health[AA021434] ; National Institutes of Health[AA020265] ; Research Scholar Grant from the American Cancer Society[RSG-13-198-01] ; V scholar award from V Foundation[00000000] ; National Basic Research Program of China (973 Program)[2014CBA02004] ; Shanghai Municipal Science and Technology Commission[15410723100] ; University of Chicago molecular and cellular biology training grant[T32] ; University of Chicago molecular and cellular biology training grant[GM007183] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000404566600012 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272571]  |
| 专题 | 化学蛋白质组学研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wu, Xiaoyang |
| 作者单位 | 1.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China; 4.Univ Louisville, Hlth Sci Ctr, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA; 5.NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY USA |
| 推荐引用方式 GB/T 7714 | Lee, Philbert,Jiang, Shangwen,Li, Yuanyuan,et al. Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis[J]. EMBO JOURNAL,2017,36(13):1963-1980. |
| APA | Lee, Philbert.,Jiang, Shangwen.,Li, Yuanyuan.,Yue, Jiping.,Gou, Xuewen.,...&Wu, Xiaoyang.(2017).Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis.EMBO JOURNAL,36(13),1963-1980. |
| MLA | Lee, Philbert,et al."Phosphorylation of Pkp1 by RIPK4 regulates epidermal differentiation and skin tumorigenesis".EMBO JOURNAL 36.13(2017):1963-1980. |
入库方式： OAI收割
来源：上海药物研究所
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