Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24.
Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24.
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DOI：
10.1038/s41467-020-20841-6
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发表时间：
2021-01-21
影响因子：
16.6
通讯作者：
Slavoff SA
中科院分区：
文献类型：
--
作者：
Cao X;Khitun A;Luo Y;Na Z;Phoodokmai T;Sappakhaw K;Olatunji E;Uttamapinant C;Slavoff SA
最近已经注释了数千个人类小的和替代的开放阅读框架（分别为smORF和alt-ORF）。许多alt-ORF与典型蛋白质以多顺反子构型共编码，但其功能知之甚少。在这里，我们报告检测alt-RPL 36，与人RPL 36共编码的蛋白质。Alt-RPL 36部分定位于内质网，在那里它与TMEM 24相互作用，TMEM 24将磷脂酰肌醇4，5-二磷酸（PI（4，5）P2）前体磷脂酰肌醇从内质网转运到质膜。敲除alt-RPL 36增加质膜PI（4，5）P2水平，上调PI 3 K-AKT-mTOR信号传导，并增加细胞大小。Alt-RPL 36含有四个磷酸丝氨酸残基，其点突变消除了与TMEM 24的相互作用，因此，alt-RPL 36对PI 3 K信号传导和细胞大小的影响。这些结果暗示alt-RPL 36是PI 3 K-AKT-mTOR信号传导的上游调节剂。更广泛地说，RPL 36转录物编码两种序列独立的多肽，它们通过不同的分子机制共同调节翻译，扩展了我们对多顺反子人类基因功能的了解。许多替代的ORF与特征蛋白共编码，但它们的功能往往不清楚。在这里，作者发现核糖体蛋白L36与替代蛋白共编码，他们将其鉴定为PI 3 K-AKT-mTOR信号传导的上游调节因子。
Thousands of human small and alternative open reading frames (smORFs and alt-ORFs, respectively) have recently been annotated. Many alt-ORFs are co-encoded with canonical proteins in multicistronic configurations, but few of their functions are known. Here, we report the detection of alt-RPL36, a protein co-encoded with human RPL36. Alt-RPL36 partially localizes to the endoplasmic reticulum, where it interacts with TMEM24, which transports the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) precursor phosphatidylinositol from the endoplasmic reticulum to the plasma membrane. Knock-out of alt-RPL36 increases plasma membrane PI(4,5)P2 levels, upregulates PI3K-AKT-mTOR signaling, and increases cell size. Alt-RPL36 contains four phosphoserine residues, point mutations of which abolish interaction with TMEM24 and, consequently, alt-RPL36 effects on PI3K signaling and cell size. These results implicate alt-RPL36 as an upstream regulator of PI3K-AKT-mTOR signaling. More broadly, the RPL36 transcript encodes two sequence-independent polypeptides that co-regulate translation via different molecular mechanisms, expanding our knowledge of multicistronic human gene functions. Many alternative ORFs are co-encoded with characterized proteins, but their function is often not understood. Here, the authors discover that ribosomal protein L36 is co-encoded with alternative protein, which they identify as an upstream regulator of PI3K-AKT-mTOR signaling.
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影响因子：
7.7
作者：
Andreev DE;O'Connor PB;Fahey C;Kenny EM;Terenin IM;Dmitriev SE;Cormican P;Morris DW;Shatsky IN;Baranov PV
通讯作者：
Baranov PV
影响因子：
7
作者：
Brunet MA;Levesque SA;Hunting DJ;Cohen AA;Roucou X
通讯作者：
Roucou X
DOI：
10.1126/science.aah6171
发表时间：
2017-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lees JA;Messa M;Sun EW;Wheeler H;Torta F;Wenk MR;De Camilli P;Reinisch KM
通讯作者：
Reinisch KM
DOI：
10.1073/pnas.0509809103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Levine, Mia T.;Jones, Corbin D.;Begun, David J.
通讯作者：
Begun, David J.
影响因子：
56.9
作者：
Chen, Jin;Brunner, Andreas-David;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.