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The large intracellular loop of ptch1 mediates the non-canonical Hedgehog pathway through cyclin B1 in nevoid basal cell carcinoma syndrome
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
2014-08-01
DOI10.3892/ijmm.2014.1783
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
WOS记录号WOS:000339127900017
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64136
专题北京大学口腔医学院_口腔病理科
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
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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.
APA Yu, Fei-Yan,Hong, Ying-Ying,Qu, Jia-Fei,Chen, Feng,&Li, Tie-Jun.(2014).The large intracellular loop of ptch1 mediates the non-canonical Hedgehog pathway through cyclin B1 in nevoid basal cell carcinoma syndrome.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,34(2),507-512.
MLA Yu, Fei-Yan,et al."The large intracellular loop of ptch1 mediates the non-canonical Hedgehog pathway through cyclin B1 in nevoid basal cell carcinoma syndrome".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34.2(2014):507-512.
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