Recent progress in the study of the Rheb family GTPases.

Recent progress in the study of the Rheb family GTPases.
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DOI:
10.1016/j.cellsig.2014.05.011
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发表时间:
2014-09
影响因子:
4.8
通讯作者:
Tamanoi F
Tamanoi F
中科院分区:
生物学2区
文献类型:
--
作者:
Heard JJ;Fong V;Bathaie SZ;Tamanoi F

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本文综述了Rheb家族GTPases的最新研究进展。使用x射线晶体学和核磁共振的结构研究使我们深入了解了这种GTPase的独特特征。结合诱变研究,这些工作扩大了我们对影响Rheb GTP/GDP结合比、效应蛋白相互作用和mTORC1信号刺激的残基的理解。对癌症基因组数据库的分析显示,几种人类癌症含有该蛋白的激活突变。Rheb在响应刺激激活溶酶体mTORC1信号传导中的作用已进一步阐明。Rheb也被认为在其他细胞途径中发挥作用,包括有丝分裂和过氧化物酶体ROS反应。许多小鼠研究已经证明Rheb在发育中的重要性,以及在包括心脏保护和髓鞘形成在内的各种功能中的重要性。最后,对Rheb家族GTPases的研究前景进行了展望。
In this review we highlight recent progress in the study of Rheb family GTPases. Structural studies using X-ray crystallography and NMR have given us insight into unique features of this GTPase. Combined with mutagenesis studies, these works have expanded our understanding of residues that affect Rheb GTP/GDP bound ratios, effector protein interactions, and stimulation of mTORC1 signaling. Analysis of cancer genome databases has revealed that several human carcinomas contain activating mutations of the protein. Rheb’s role in activating mTORC1 signaling at the lysosome in response to stimuli has been further elucidated. Rheb has also been suggested to play roles in other cellular pathways including mitophagy and peroxisomal ROS response. A number of studies in mice have demonstrated the importance of Rheb in development, as well as in a variety of functions including cardiac protection and myelination. We conclude with a discussion of future prospects in the study of Rheb family GTPases.
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