Dataset Information

Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.

ABSTRACT: p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here that TAp63 phosphorylated at T46/T281 specifically upregulates the late cornified envelope 1C (LCE1C) gene that is essential at a relatively late stage of epithelial development. We identified these phosphorylation sites during a search for the targets of Cyclin G-associated kinase (GAK) in vitro. LCE1C was drastically upregulated by doxycycline-dependent expression of Myc-TAp63 wild-type protein. Luciferase reporter assays using the promoter region of the LCE1C gene confirmed that the phosphorylations of TAp63-T46/T281 contributed to full transcriptional activation of the LCE1C gene. LCE1C interacted with protein arginine methyltransferase 5 (PRMT5) and translocated it from the nucleus to the cytoplasm. Mass spectrometry and co-immunoprecipitation identified importin-? as one of the association partners of LCE1C. In summary, we propose that the GAK_TAp63-pT46/pT281_LCE1C axis plays an important role in preventing the nuclear function of PRMT5.

SUBMITTER: Yabuta N

PROVIDER: S-EPMC5861035 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.

Yabuta Norikazu N Ota Chie C Sasakura Towa T Naito Yoko Y Okuzaki Daisuke D Fukushima Kohshiro K Nojima Hiroshi H

Scientific reports 20180320 1

p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here that TAp63 phosphorylated at T46/T281 specifically upregulates the late cornified envelope 1C (LCE1C) gene that is essential at a relatively late stage of epithelial development. We identified these phosphorylation sites during a search for the targets of Cyclin G-associ ...[more]

PMID: 29559659

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Project description:PurposePsoriasis is a common cutaneous disease with multiple characteristics including inflammation and aberrant keratinocyte proliferation. However, the pathogenesis of psoriasis is not completely clear yet. The objective of this study is to perform an in-depth analysis of the association between SPRR and LCE in the pathogenesis of psoriasis.MethodsIn this study, we explore the differentially expressed genes (DEGs) in psoriasis by analyzing different gene expression profiles obtained from the Gene Expression Omnibus (GEO) database. The DEGs were examined using gene ontology (GO) functional enrichment analysis and protein-protein interactions (PPI) network. Correlation analysis in R studio software was used to analyze the association between SPRR and LCE genes. Further, potential direct protein-protein interactions between SPRR proteins and LCE3D were verified by co-localization observations and co-immunoprecipitation (CO-IP) assays in 293T cells. Also, the expression levels of SPRR and LCE genes were detected in lesional skin of the IMQ-induced psoriasiform dermatitis mice using RT-PCR.ResultsInterestingly, the small proline-rich (SPRR) and late cornified envelope (LCE) genes were identified as a module in the constructed PPI network. And the analysis of the gene expression profile GSE63684 showed that both SPRR family and LCE family genes were significantly upregulated in imiquimod (IMQ) induced psoriasiform dermatitis mice. Also, the correlation analysis in R studio software recognized the association of SPRR and LCE genes, which were further verified by co-localization and co-immunoprecipitation (CO-IP) assays in 293T cells, and the results show that the direct interactions between SPRR2 and LCE3D. Notably, we also found that the expression levels of SPRR and LCE genes were significantly increased in the IMQ-induced psoriasiform dermatitis mice, while specifically decreased under the tazarotene cream treatment, indicating that the SPRR and LCEs were regulated simultaneously in psoriasis.ConclusionIn summary, our study found that interactions between SPRR proteins and LCE proteins may provide new insights into the pathogenesis of psoriasis.

Dataset Information

Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.

Publications

Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.

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