Chorein interacts with alpha-tubulin and HDAC6, and overexpression preserves cell viability during nutrient deprivation in HEK293 cells

Chorein interacts with alpha-tubulin and HDAC6, and overexpression preserves cell viability during nutrient deprivation in HEK293 cells
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Chorein 与 α-微管蛋白和 HDAC6 相互作用,过度表达可在 HEK293 细胞营养缺乏期间保持细胞活力

DOI:
10.1096/fj.201500191rr
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发表时间:
2016
期刊:
影响因子:
4.8
通讯作者:
Sano A
Sano A
中科院分区:
生物学2区
文献类型:
--
作者:
Sasaki N;Nakamura M;Kodama A;Urata Y;Shiokawa N;Hayashi T;Sano A

文献摘要

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自噬通路最近被认为与几种神经退行性疾病有关。最近,据报道,软骨素耗尽的细胞显示自噬标记物的积累和受损的自噬通量。在这里,我们证明了在人胚肾293(HEK 293)细胞中,chorein过表达保护了细胞活力免于饥饿诱导的细胞死亡。随后使用稳定过表达HEK 293细胞的chorein提取物进行的免疫共沉淀和反向免疫共沉淀试验显示,chorein与α-微管蛋白和组蛋白脱乙酰酶6相互作用,后者是一种已知的α-微管蛋白脱乙酰酶和基础自噬的中心组分。事实上,乙酰化α微管蛋白免疫反应性在稳定过表达HEK 293细胞的chorein中显著降低。这些结果表明,舞蹈蛋白/组蛋白去乙酰化酶6/α-微管蛋白的相互作用可能在饥饿诱导的细胞应激中发挥重要作用,它们的破坏可能是舞蹈病棘红细胞增多症的分子致病机制之一。Sasaki,N.,中村,M.,Kodama,A.,Urata,Y.,Shiokawa,N.,Hayashi,T.,佐野,A. Chorein与α-微管蛋白和组蛋白去乙酰化酶6相互作用,并且在人胚肾293细胞的营养剥夺期间过表达保留细胞活力。FASEB J. 30,3726-3732(2016)www.fasebj.org
The autophagy pathway has recently been implicated in several neurodegenerative diseases. Recently, it was reported that chorein‐depleted cells showed accumulation of autophagic markers and impaired autophagic flux. Here, we demonstrate that chorein overexpression preserves cell viability from starvation‐induced cell death in human embryonic kidney 293 (HEK293) cells. Subsequent coimmunoprecipitation and reverse coimmunoprecipitation assays using extracts from chorein that stably overexpressed HEK293 cells revealed that chorein interacts with α‐tubulin and histone deacetylase 6, a known α‐tubulin deacetylater and central component of basal autophagy. Indeed, acetylated α‐tubulin immunoreactivity was significantly decreased in chorein that stably overexpressed HEK293 cells. These results suggest that chorein/histone deacetylase 6/α‐tubulin interactions may play an important role in starvation‐induced cell stress, and their disruption may be one of the molecular pathogenic mechanisms of chorea‐acanthocytosis.—Sasaki, N., Nakamura, M., Kodama, A., Urata, Y., Shiokawa, N., Hayashi, T., Sano, A. Chorein interacts with α‐tubulin and histone deacetylase 6, and overexpression preserves cell viability during nutrient deprivation in human embryonic kidney 293 cells. FASEB J. 30, 3726–3732 (2016) www.fasebj.org