Zyxin is a novel interacting partner for SIRT1.

Zyxin is a novel interacting partner for SIRT1.
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DOI:
10.1186/1471-2121-10-6
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发表时间:
2009-01-27
期刊:
影响因子:
--
通讯作者:
Yamashita T
Yamashita T
中科院分区:
生物3区
文献类型:
--
作者:
Fujita Y;Yamaguchi A;Hata K;Endo M;Yamaguchi N;Yamashita T

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SIRT 1是NAD+依赖性去乙酰化酶sirtuin家族的哺乳动物同源物。它调节几种模式生物的寿命,并参与哺乳动物细胞中的细胞存活、分化、代谢等过程。SIRT 1通过去乙酰化调节各种关键靶点的功能。最近的研究表明,SIRT 1保护神经元免于轴突变性或神经变性。此外,SIRT 1敲除小鼠表现出生长迟缓和发育缺陷,表明其在神经元和发育中的关键作用。为了寻找SIRT 1在中枢神经系统中的新的结合伙伴,我们利用酵母双杂交技术对人胎脑cDNA文库进行了筛选,发现zyxin是SIRT 1的一个可能的结合伙伴。SIRT 1和zyxin转录本均优先在发育期小鼠脑中表达。在COS-7细胞中,用来普霉素B处理后,Zyxin在细胞核中积累,在那里它与SIRT 1共定位。此外,SIRT 1还能使zyxin脱乙酰化,表明SIRT 1可以与核积累的zyxin相互作用,并通过脱乙酰化调节其功能。Zyxin可能是SIRT 1的一个新的相互作用伙伴。Zyxin是粘着斑处的衔接蛋白,调节细胞骨架动力学和信号转导以将信号从ECM(细胞外基质)传递到细胞核。我们的研究结果提出了SIRT 1通过去乙酰化调节zyxin的功能来调节ECM向细胞核的信号传递的可能性。
SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development. To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation. Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.
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