更新于：2024-05-01

PRR5

proline rich 5

更新于：2024-05-01

基本信息

别名

FLJ20185k、PP610、proline rich 5

+ [5]

简介

Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling. May act as a tumor suppressor in breast cancer.

关联

100 项与 PRR5 相关的临床结果

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100 项与 PRR5 相关的转化医学

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0 项与 PRR5 相关的专利（医药）

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109

项与 PRR5 相关的文献（医药）

2024-02-22·Planta

Unlocking allelic variation in circadian clock genes to develop environmentally robust and productive crops.

Review

作者: Sangam Lal Dwivedi ; Luis Felipe Quiroz ; Charles Spillane ; Rongling Wu ; Autar K Mattoo ; Rodomiro Ortiz

MAIN CONCLUSION:

Molecular mechanisms of biological rhythms provide opportunities to harness functional allelic diversity in core (and trait- or stress-responsive) oscillator networks to develop more climate-resilient and productive germplasm. The circadian clock senses light and temperature in day-night cycles to drive biological rhythms. The clock integrates endogenous signals and exogenous stimuli to coordinate diverse physiological processes. Advances in high-throughput non-invasive assays, use of forward- and inverse-genetic approaches, and powerful algorithms are allowing quantitation of variation and detection of genes associated with circadian dynamics. Circadian rhythms and phytohormone pathways in response to endogenous and exogenous cues have been well documented the model plant Arabidopsis. Novel allelic variation associated with circadian rhythms facilitates adaptation and range expansion, and may provide additional opportunity to tailor climate-resilient crops. The circadian phase and period can determine adaptation to environments, while the robustness in the circadian amplitude can enhance resilience to environmental changes. Circadian rhythms in plants are tightly controlled by multiple and interlocked transcriptional-translational feedback loops involving morning (CCA1, LHY), mid-day (PRR9, PRR7, PRR5), and evening (TOC1, ELF3, ELF4, LUX) genes that maintain the plant circadian clock ticking. Significant progress has been made to unravel the functions of circadian rhythms and clock genes that regulate traits, via interaction with phytohormones and trait-responsive genes, in diverse crops. Altered circadian rhythms and clock genes may contribute to hybrid vigor as shown in Arabidopsis, maize, and rice. Modifying circadian rhythms via transgenesis or genome-editing may provide additional opportunities to develop crops with better buffering capacity to environmental stresses. Models that involve clock gene‒phytohormone‒trait interactions can provide novel insights to orchestrate circadian rhythms and modulate clock genes to facilitate breeding of all season crops.

2024-01-21·International journal of molecular sciences

Transcriptomic and Phenotypic Analyses Reveal the Molecular Mechanism of Dwarfing in Tetraploid Robinia pseudoacacia L.

Article

作者: Yue Wu ; Qi Guo ; Cui Long ; Yousry A El-Kassaby ; Yuhan Sun ; Yun Li

Polyploid breeding techniques aid in the cultivation of new forestry cultivars, thus expanding the suite of strategies for the improvement of arboreal traits and innovation within the field of forestry. Compared to diploid Robinia pseudoacacia L. (black locust) 'D26-5①' (2×), its dwarfed homologous tetraploid 'D26-5②' (4×) variety has better application prospects in garden vegetation guardrails and urban landscape. However, the molecular mechanism of the generation and growth of this dwarf variety is still unclear. Here, plant growth and development as well as histological differences between the diploid and its autotetraploid were investigated. Levels of endogenous hormones at three different developmental stages (20, 40, and 70 days) of 2× and homologous 4× tissue culture plantlets were assessed, and it was found that the brassinosteroid (BR) contents of the former were significantly higher than the latter. Transcriptome sequencing data analysis of 2× and homologous 4× showed that differentially expressed genes (DEGs) were significantly enriched in plant hormone synthesis and signal transduction, sugar and starch metabolism, and the plant circadian rhythm pathway, which are closely related to plant growth and development. Therefore, these biological pathways may be important regulatory pathways leading to dwarfism and slow growth in tetraploids. Additionally, utilizing weighted gene coexpression network analysis (WGCNA), we identified three crucial differentially expressed genes (DEGs)-PRR5, CYP450, and SPA1-that potentially underlie the observed ploidy variation. This study provides a new reference for the molecular mechanism of dwarfism in dwarfed autotetraploid black locusts. Collectively, our results of metabolite analysis and comparative transcriptomics confirm that plant hormone signaling and the circadian rhythm pathway result in dwarfism in black locusts.

2023-10-26·International urology and nephrology

Multi-omics analysis reveals critical metabolic regulators in bladder cancer.

Article

作者: Chengcheng Wei ; Changqi Deng ; Rui Dong ; Yaxin Hou ; Miao Wang ; Liang Wang ; Teng Hou ; Zhaohui Chen

BACKGROUND:

The crosstalk between genomic alterations and metabolic dysregulation in bladder cancer is largely unknown. A deep understanding of the interactions between cancer drivers and cancer metabolic changes will provide novel opportunities for targeted therapeutic strategies.

METHODS:

Three primary bladder cancer specimens with paired normal tissues or blood samples were subjected to whole-exome sequencing, DNA methylation array and whole-transcriptome sequencing by next-generation sequencing technology. We applied the methods to multi-omics data combining the Cancer Genome Atlas (TCGA) bladder cancer samples, including somatic mutation, DNA copy number, DNA methylation and gene expression profile for validation.

RESULTS:

We identified 34 mutated cancer driver genes in bladder cancer. KDM6A was the most significantly mutated cancer driver gene. Metabolic pathways were enriched in both differentially methylated regions (DMRs) and differentially expressed genes. Twenty-nine DMRs in the TSS200 region were highly correlated with the upregulation of gene expression, and 24 DMRs in the genome were highly correlated with the downregulation of gene expression. A total of 201 genes had highly correlated DNA methylation and expression. Thirty-four genes, including the known metabolic genes CXXC5, PRR5, ABCB8 and BAHD1, were further validated in the TCGA cohort. Multi-omics alterations identified two new candidate driver genes, WIPI2 and GFM2, that warrant future studies.

CONCLUSIONS:

This study provides a comprehensive and systematic analysis, focusing on identifying key regulatory factors that may lead to cancer metabolic heterogeneity. Further understanding and verification of the cancer genes driving metabolic reprogramming and their role in the progression of bladder cancer will help to identify new therapeutic targets.

项与 PRR5 相关的新闻（医药）

2024-03-20

·生物谷

研究揭示剪接体进行分支位点选择、校正的分子机理

本研究为理解剪接体的早期组装过程以及分支位点的识别和选择机制提供了重要的结构信息，同时也为与癌症相关的SF3B1突变的致病机制提供了新的见解。西湖大学施一公团队在《自然结构与分子生物学》（Nature Structural and Molecular Biology）在线发表了题为“Structural Insights into Branch Site Proofreading by Human Spliceosome”的最新研究论文，报道了人源17S U2 snRNP复合物和剪接体pre-A复合物的高分辨率结构，并结合生化和功能实验，揭示了剪接体进行分支位点选择、校正的分子机理。

基因疗法

2024-01-11

·生物谷

Nature子刊 | 西湖大学施一公团队揭示剪接体进行分支位点选择、校正的分子机理

北京时间2024年1月9日，西湖大学施一公团队在《自然结构与分子生物学》（Nature Structural and Molecular Biology）在线发表了题为“Structural Insights into Branch Site Proofreading by Human Spliceosome”的最新研究论文，报道了人源17S U2 snRNP复合物和剪接体pre-A复合物的高分辨率结构，并结合生化和功能实验，揭示了剪接体进行分支位点选择、校正的分子机理。mRNA剪接是真核生物基因表达的关键步骤，由剪接体催化完成。剪接体是一个巨大且高度动态的分子机器，其核心组成元件为5种核内小核糖核蛋白复合物（snRNP），分别为U1，U2，U4，U5和U6 snRNP。剪接体通过识别pre-mRNA上保守的剪接位点完成早期的组装。首先，U1 snRNP识别5'剪接位点，剪接因子SF1识别分支位点（branch site, BS），形成E complex。随后，U2 snRNP替换SF1，识别分支位点，并且U2 snRNA与分支位点形成RNA双螺旋，完成A complex的组装1。在高等真核生物中，大部分基因都会发生可变剪接，这个过程需要剪接体选择不同的剪接位点。因此，研究这些早期复合物对于理解剪接反应的保真性和调控机制至关重要。近些年，随着冷冻电镜技术的突破，一系列人源和酵母的剪接体复合物结构获得解析，极大地促进了人们对mRNA剪接分子机制的认识2-5。但由于剪接反应早期的复合物具有高度的动态性和不稳定性，其结构研究进展缓慢。研究人员首先通过PRP5上引入的FLAG标签纯化出内源的17S U2 snRNP并解析了整体分辨率达到2.5 Å的电镜结构。随后通过使用exon-definition的pre-mRNA底物和小分子抑制剂spliceostatin A (SSA)，成功捕获了一个介于E和A complex之间的中间反应状态，命名为pre-A复合物。Pre-A复合物主要包含两个区域：U2 snRNP区域和U1 snRNP区域。其中U1 snRNP非常柔性，未能解析到较高的分辨率，而U2 snRNP区域整体分辨率达到3Å，可以搭建原子模型（图1）。图1: 17S U2 snRNP和pre-A复合物的电镜结构在17S U2 snRNP中PRP5主要通过其N端锚定在SF3B1外围，其中acidic loop占据了SF3B1的RNA通道，而它的解旋酶结构域则结合在U2 snRNA附近。剪接因子TAT-SF1通过其Linker domain将U2 snRNA的BS-interacting stem loop （BSL）包裹起来，从而避免BSL过早打开以及结合pre-mRNA。在pre-A复合物中，SF3B1仍然处于开放状态，PRP5的acidic loop依然结合在SF3B1的RNA通道中，但其解旋酶结构域发生了显著的构象变化。与之相应的，TAT-SF1从复合物中解离，并且U2 snRNA和pre-mRNA通过部分的互补配对，形成了一个初始的双链结构（initial U2/BS duplex）。剪接因子SF1和DNAJC8稳定了局部的构象。同先前报道的剪接反应抑制剂E7107一样6， SSA也结合在SF3B1和PHF5A形成的铰链口袋（hinged pocket）中。不同的是，SSA与PHF5A第26位的半胱氨酸形成了共价键。由于SSA的结合，导致分支位点腺苷（BS-A）无法进入铰链口袋而游离在外面。与此同时，分支位点下游的多聚嘧啶区（polypyrimidine tract）也没有替换PRP5的acidic loop结合到SF3B1的RNA通道path中。据此，研究人员推测，BS-A进入铰链口袋是诱发SF3B1从开放到关闭构象变化的初始条件，而伴随着SF3B1的构象变化，PRP5、SF1以及DNAJC8会发生解离，SF3B1紧紧包裹住pre-mRNA，从而完成U2 snRNP对分支位点的选择，形成A complex（图2）。在这个过程中， PRP5的acidic loop与PPT竞争结合SF3B1的RNA通道是PRP5行使其校正功能的关键。图2: 17S U2 snRNP到A complex过程中的结构变化以及PRP5校正U2/BS duplex的模型图值得关注的是，研究人员发现PRP5的acidic loop与SF3B1的结合界面上，分布着大量与癌症相关的突变位点。结合先前对PRP5功能7和癌症患者中剪接异常现象8的研究，研究人员推测这些突变可能是通过削弱PRR5的结合，影响其对分支位点的校正功能，进而引发剪接异常，导致疾病的发生。研究人员的生化和RNA-seq数据支持了这种观点。总的来说，本研究为理解剪接体的早期组装过程以及分支位点的识别和选择机制提供了重要的结构信息，同时也为与癌症相关的SF3B1突变的致病机制提供了新的见解。文章链接：https://www-nature-com.libproxy1.nus.edu.sg/articles/s41594-023-01188-0本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

信使RNA

2023-08-14

·生物谷

研究揭示组蛋白去乙酰化酶MdHDA6调控苹果响应低温胁迫的分子机制

综上，MdHDA6-MdTCP15模块对苹果低温相关基因的新调节机制：（1）MdTCP15 依靠其DNA结合能力，MdTCP15招募MdHDA6至靶基因 MdABI1，使MdHDA6对MdABI1基因近日，西北农林科技大学园艺学院旱区作物逆境生物学国家重点实验室管清美/徐记迪课题组在Plant Biotechnology Journal上发表了题为“Histone deacetylase MdHDA6 is an antagonist in regulation of transcription factor MdTCP15 to promote cold tolerance in apple”的研究论文，揭示了组蛋白去乙酰化酶MdHDA6在调控MdTCP15诱导的转录激活或抑制中起拮抗作用，以正向调控苹果耐寒性，揭示了MdHDA6-MdTCP15模块调控苹果响应低温胁迫的分子机制。低温对苹果树生长易造成严重威胁，特别在开花期间影响其坐果率，果实生产力造成巨大损失。因此，揭示苹果植物响应低温胁迫的分子机制使我们能够利用调节机制进行作物改良。为探究 MdHDA6 在苹果低温胁迫下的调控作用，本研究获得了MdHDA6过表达（ MdHDA6 -OE）和RNA干扰（ MdHDA6 -RNAi）苹果转基因系，并进行低温处理。结果显示 MdHDA6 -OE植株表现出更强的抗寒性，而沉默株系则更敏感。众所周知，组蛋白去乙酰化可以收紧染色质结构并最终抑制基因表达。因此作者选择了四个低温负调控因子（ PRR5 ， NAC029 ， ABI1 和 PIF3 ），并通过ChIP-qPCR以验证其H3ac水平，发现MdHDA6促进低温相关基因的组蛋白去乙酰化，并抑制其表达，正向调控苹果的抗寒性。 MdHDA6是一种催化酶，不具有结合下游基因的能力。有研究报道HDAs可以直接与转录因子（TFs）相互作用，并依靠转录因子的结合能力靶向下游基因。随后，研究发现MdHDA6与转录因子MdTCP15相互作用，并促进MdTCP15上的组蛋白去乙酰化并抑制其表达。因此，探索MdTCP15在苹果对冷胁迫反应中的调节作用，过表达 MdTCP15 降低了苹果的耐寒性。相比之下， MdTCP15 -RNAi株系在低温处理下与GL-3植物相比显示出更强的耐寒性。进一步研究发现，MdTCP15可以激活低温负调控因子表达，并抑制低温正调控因子，从而负向调节苹果的耐寒性。由于MdTCP15是一种转录因子，因此可以直接与下游靶基因结合，对其靶基因进行转录调控。通过ChIP-qPCR和EMSA验证发现MdTCP15与MdABI1和MdCOR47启动子结合，Dual-luc实验进一步说明MdTCP15可以激活MdABI1的表达，抑制MdCOR47的表达，然而共同表达MdHDA6和MdTCP15后发现，MdHDA6通过直接与MdTCP15相互作用来抑制MdTCP15对靶基因的转录调控。综上，MdHDA6-MdTCP15模块对苹果低温相关基因的新调节机制：（1）MdTCP15 依靠其DNA结合能力，MdTCP15招募MdHDA6至靶基因 MdABI1，使MdHDA6对MdABI1基因组区域进行组蛋白去乙酰化，抑制其表达，增强耐寒性；（2）MdHDA6的参与抑制了MdTCP15对冷低温负调控因子 MdABI1 的激活，从而增强了耐寒性；（3）MdHDA6的参与抑制了MdTCP15对MdCOR4表达的抑制，这对苹果耐寒性有积极调控作用。徐记迪副教授为论文的通讯作者，硕士生郭美苗为论文第一作者，该项目得到了国家自然科学基金、陕西省重大科技专项、陕西省人才引进专项的资助。