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学科主题: 口腔医学
题名:
The large intracellular loop of ptch1 mediates the non-canonical Hedgehog pathway through cyclin B1 in nevoid basal cell carcinoma syndrome
作者: Yu, Fei-Yan1; Hong, Ying-Ying1; Qu, Jia-Fei1; Chen, Feng2; Li, Tie-Jun1
关键词: nevoid basal cell carcinoma syndrome ; non-canonical Hedgehog pathway ; cyclin B1 ; ptch1
刊名: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
发表日期: 2014-08-01
DOI: 10.3892/ijmm.2014.1783
卷: 34, 期:2, 页:507-512
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: KERATOCYSTIC ODONTOGENIC-TUMORS ; SONIC HEDGEHOG ; M-PHASE ; PHOSPHORYLATION ; MUTATIONS ; GENE ; SIGNAL ; LOCALIZATION ; HOMOLOG
英文摘要:

Mutations in the transmembrane receptor patched homolog 1 (Homo sapiens) (ptch1) are responsible for nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder that causes developmental abnormalities and predisposes the affected individuals to cancer. Many of these mutations, including mutations in the C-terminus of the large intracellular loop (ICL) of ptch1 (p.C727VfsX745 and p.S733IfsX736), result in the premature truncation of the protein. The ptchl-C727VfsX745 and ptch1-S733IfsX736 mutations have been identified in patients with NBCCS-associated keratocystic odontogenic tumors (KCOTs). In the present study, we found that the molecular mechanisms regulated by the non-canonical Hedgehog (Hh) signaling pathway through cyclin B1 are involved in the pathogenesis of NBCCS-associated KCOTs. In contrast to wild-type ptch1, ptch1-C727VfsX745 and ptchl-S733IfsX736 clearly exhibited reduced binding to cyclin B1. Moreover, the cells expressing these two mutations demonstrated an increase in cell cycle progression and these two mutation constructs failed to inhibit cell proliferation. In addition, the mutants enhanced the activity of glioma-associated oncogene family zinc finger 1 (GLI1), a downstream reporter of Hh signaling. Thus, our data suggest that the non-canonical Hh pathway mediated through ptch1 and cyclin B1 is involved in the pathogenesis of NBCCS-associated KCOTs. The C-terminus of ICL in ptch1 may also be a potential therapeutic target in the treatment of this disease.

语种: 英语
所属项目编号: 81030018 ; 20130001110043
项目资助者: National Natural Science Foundation of China ; Ministry of Education of China
WOS记录号: WOS:000339127900017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64136
Appears in Collections:北京大学口腔医学院_口腔病理科_期刊论文

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作者单位: 1.Peking Univ, Sch & Hosp Stomatol, Dept Oral Pathol, Beijing 100081, Peoples R China
2.Peking Univ, Sch & Hosp Stomatol, Cent Lab, Beijing 100081, Peoples R China

Recommended Citation:
Yu, Fei-Yan,Hong, Ying-Ying,Qu, Jia-Fei,et al. The large intracellular loop of ptch1 mediates the non-canonical Hedgehog pathway through cyclin B1 in nevoid basal cell carcinoma syndrome[J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2014,34(2):507-512.
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