调节转录的LAP2蛋白 GLI1 运动在膜和染色体之间
Amar N Mirza1, Siegen A McKellar1, Nicole M Urman1
1Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|December 4, 2018
概括
一种新型的核辅导系统涉及膜相关聚2 (LAP2) 异型,调节基底细胞癌中的GLI1运动. 这种系统会影响子通路的信号传输,
科学领域:
- 细胞生物学
- 分子生物学
- 癌症研究
背景情况:
- 在基底细胞癌 (BCC) 中,转录因子GLI1对子通路输出至关重要.
- 耐药BCC通过非典型蛋白激酶Cι/λ (aPKC) 和HDAC1增加了GLI1脱乙烯化.
- 了解GLI1核传输对于向癌症治疗至关重要.
研究的目的:
- 确定控制GLI1内核运动的核监护系统.
- 阐明膜相关聚2 (LAP2) 异型在 GLI1 贩运和激活中的作用.
- 探索对BCC信号传导和治疗策略的影响.
主要方法:
- 研究了GLI1和LAP2异型 (LAP2α和LAP2β) 之间的相互作用.
- 研究了aPKC和HDAC1在GLI1脱乙和核运输中的影响.
- 研究了与核膜和核质相关的GLI1定位和活性.
主要成果:
- 确定了一种依赖LAP2异型的系统来控制GLI1的核转移.
- LAP2β将GLI1与核膜结合,形成一种依赖于乙化的储备.
- 与LAP2α竞争,与HDAC1进行支架,并与aPKC促进GLI1释放以激活核质.
结论:
- LAP2 异型在内核膜和核质之间差异调节 GLI1 核流通.
- 这种LAP2介导系统作为BCC中的GLI1的信号放大器.
- 针对GLI1内核贩运为BCC提供了潜在的治疗途径.
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