气候变化领域集成服务门户(CCPortal): Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy

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DOI	10.1073/pnas.2024502118
	Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy
	Lombardi A.; Arseni L.; Carriero R.; Compe E.; Botta E.; Ferri D.; Uggè M.; Biamonti G.; Peverali F.A.; Bione S.; Orioli D.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:26
英文摘要	The cancer-free photosensitive trichothiodystrophy (PS-TTD) and the cancer-prone xeroderma pigmentosum (XP) are rare monogenic disorders that can arise from mutations in the same genes, namely ERCC2/XPD or ERCC3/XPB. Both XPD and XPB proteins belong to the 10-subunit complex transcription factor IIH (TFIIH) that plays a key role in transcription and nucleotide excision repair, the DNA repair pathway devoted to the removal of ultravioletinduced DNA lesions. Compelling evidence suggests that mutations affecting the DNA repair activity of TFIIH are responsible for the pathological features of XP, whereas those also impairing transcription give rise to TTD. By adopting a relatives-based whole transcriptome sequencing approach followed by specific gene expression profiling in primary fibroblasts from a large cohort of TTD or XP cases with mutations in ERCC2/XPD gene, we identify the expression alterations specific for TTD primary dermal fibroblasts. While most of these transcription deregulations do not impact on the protein level, very low amounts of prostaglandin I2 synthase (PTGIS) are found in TTD cells. PTGIS catalyzes the last step of prostaglandin I2 synthesis, a potent vasodilator and inhibitor of platelet aggregation. Its reduction characterizes all TTD cases so far investigated, both the PS-TTD with mutations in TFIIH coding genes as well as the nonphotosensitive (NPS)-TTD. A severe impairment of TFIIH and RNA polymerase II recruitment on the PTGIS promoter is found in TTD but not in XP cells. Thus, PTGIS represents a biomarker that combines all PS- and NPS-TTD cases and distinguishes them from XP. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	NER-defective disorders; PTGIS; TFIIH transcription
语种	英语
scopus关键词	angiopoietin related protein 4; antiinfective agent; environmental mutagen; interferon; interstitial collagenase; prostacyclin synthase; prostaglandin; RNA polymerase II; transcription factor IIH; transcriptome; transforming growth factor beta; vasculotropin; xeroderma pigmentosum group D protein; cytochrome P450; prostacyclin; PTGIS protein, human; Article; cancer free survival; cancer susceptibility; cell proliferation; child; chondrocyte; clinical article; computer model; controlled study; DNA repair; excision repair; female; frameshift mutation; gene expression profiling; gene expression regulation; gene frequency; gene mutation; gene ontology; genetic disorder; human; human cell; immunoblotting; immunoprecipitation; melanoma; mouse; nail dysplasia; nonhuman; polarization microscopy; promoter region; protein expression; protein synthesis; real time polymerase chain reaction; RNA sequencing; skin cancer; thrombocyte aggregation; trichothiodystrophy; ultraviolet irradiation; ultraviolet radiation; upregulation; whole exome sequencing; whole transcriptome sequencing; xeroderma pigmentosum; animal; cell culture; enzymology; fibroblast; gene expression profiling; genetic transcription; genetics; metabolism; neoplasm; pathology; radiation response; skin; trichothiodystrophy; Animals; Cells, Cultured; Cytochrome P-450 Enzyme System; Epoprostenol; Fibroblasts; Gene Expression Profiling; Gene Expression Regulation; Mice; Neoplasms; Skin; Transcription, Genetic; Trichothiodystrophy Syndromes; Ultraviolet Rays; Xeroderma Pigmentosum
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251144
作者单位	Istituto di Genetica Molecolare L.L. Cavalli Sforza, Consiglio Nazionale delle Ricerche, Pavia, 27100, Italy; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, Strasbourg, 67404, France
推荐引用方式 GB/T 7714	Lombardi A.,Arseni L.,Carriero R.,et al. Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy[J],2021,118(26).
APA	Lombardi A..,Arseni L..,Carriero R..,Compe E..,Botta E..,...&Orioli D..(2021).Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy.Proceedings of the National Academy of Sciences of the United States of America,118(26).
MLA	Lombardi A.,et al."Reduced levels of prostaglandin I2 synthase: A distinctive feature of the cancer-free trichothiodystrophy".Proceedings of the National Academy of Sciences of the United States of America 118.26(2021).