scholarly journals TOR and RPS6 transmit light signals to enhance protein translation in deetiolating Arabidopsis seedlings

2018 ◽  
Vol 115 (50) ◽  
pp. 12823-12828 ◽  
Author(s):  
Guan-Hong Chen ◽  
Ming-Jung Liu ◽  
Yan Xiong ◽  
Jen Sheen ◽  
Shu-Hsing Wu
Keyword(s):  
Developmental Process ◽  
Protein Translation ◽  
Negative Regulator ◽  
Young Plant ◽  
Vegetative Development ◽  
Ribosomal Protein S6 ◽  
Light Signals ◽  
Photosynthetic Activities ◽  
Plant Seedlings ◽  
Mechanistic View

Deetiolation is an essential developmental process transforming young plant seedlings into the vegetative phase with photosynthetic activities. Light signals initiate this important developmental process by triggering massive reprogramming of the transcriptome and translatome. Compared with the wealth of knowledge of transcriptional regulation, the molecular mechanism underlying this light-triggered translational enhancement remains unclear. Here we show that light-enhanced translation is orchestrated by a light perception and signaling pathway composed of photoreceptors, CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1), the phytohormone auxin, target of rapamycin (TOR), and ribosomal protein S6 (RPS6). In deetiolating Arabidopsis seedlings, photoreceptors, including phytochrome A and cryptochromes, perceive far-red and blue light to inactivate the negative regulator COP1, which leads to activation of the auxin pathway for TOR-dependent phosphorylation of RPS6. Arabidopsis mutants defective in TOR, RPS6A, or RPS6B exhibited delayed cotyledon opening, a characteristic of the deetiolating process to ensure timely vegetative development of a young seedling. This study provides a mechanistic view of light-triggered translational enhancement in deetiolating Arabidopsis.

scholarly journals Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase

2021 ◽  
Vol 8 ◽  
Author(s):  
Darby J. Ballard ◽  
Hao-Yun Peng ◽  
Jugal Kishore Das ◽  
Anil Kumar ◽  
Liqing Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Elongation Factor ◽  
Protein Translation ◽  
Negative Regulator ◽  
Translation Elongation ◽  
Elongation Factor 2 ◽  
Global Rate ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor

Eukaryotic Elongation Factor-2 Kinase (eEF2K) acts as a negative regulator of protein synthesis, translation, and cell growth. As a structurally unique member of the alpha-kinase family, eEF2K is essential to cell survival under stressful conditions, as it contributes to both cell viability and proliferation. Known as the modulator of the global rate of protein translation, eEF2K inhibits eEF2 (eukaryotic Elongation Factor 2) and decreases translation elongation when active. eEF2K is regulated by various mechanisms, including phosphorylation through residues and autophosphorylation. Specifically, this protein kinase is downregulated through the phosphorylation of multiple sites via mTOR signaling and upregulated via the AMPK pathway. eEF2K plays important roles in numerous biological systems, including neurology, cardiology, myology, and immunology. This review provides further insights into the current roles of eEF2K and its potential to be explored as a therapeutic target for drug development.

scholarly journals Modulation of the Cell Growth Regulator mTOR by Epstein-Barr Virus-Encoded LMP2A

2005 ◽  
Vol 79 (9) ◽  
pp. 5499-5506 ◽  
Author(s):  
Cary A. Moody ◽  
Rona S. Scott ◽  
Nazanin Amirghahari ◽  
Cherie-Ann Nathan ◽  
Lawrence S. Young ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Mammalian Target Of Rapamycin ◽  
Human Tumor ◽  
Protein Translation ◽  
Negative Regulator ◽  
Initiation Factor ◽  
Barr Virus ◽  
Eukaryotic Initiation Factor 4E ◽  
Tumor Virus ◽  
Epstein Barr

ABSTRACT Control of translation initiation is one means by which cells regulate growth and proliferation, with components of the protein-synthesizing machinery having oncogenic potential. Expression of latency protein LMP2A by the human tumor virus Epstein-Barr virus (EBV) activates phosphatidylinositol 3-kinase/Akt located upstream of an essential mediator of growth signals, mTOR (mammalian target of rapamycin). We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Intervention by this DNA tumor virus in cellular translational controls is likely to be an integral component of EBV tumorigenesis.

scholarly journals Interaction of BIR2/3 of XIAP with E2F1/Sp1 Activates MMP2 and Bladder Cancer Invasion by Inhibiting Src Translation

2018 ◽  
Author(s):  
Jiheng Xu ◽  
Honglei Jin ◽  
Jingxia Li ◽  
Junlan Zhu ◽  
Xiaohui Hua ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Ectopic Expression ◽  
Direct Interaction ◽  
Protein Translation ◽  
Negative Regulator ◽  
Human Bladder ◽  
Design Synthesis ◽  
Cell Behaviors ◽  
Apoptosis Protein ◽  
Insight Into

AbstractAlthough X-linked inhibitor of apoptosis protein (XIAP) is associated with cancer cell behaviors, the structure-based function of XIAP in promotion human bladder cancer (BC) invasion is barely explored. Herein, we discovered that ectopic expression of the BIR domains of XIAP rescued the MMP2 activation and invasion in XIAP-deleted BC cells, while Src was further defined as a XIAP downstream negative regulator for MMP2 activation and BC invasion. The inhibition of Src expression by BIR domains was caused by attenuation of Src protein translation upon miR-203 upregulation resulting from direct interaction of BIR2 and BIR3 with E2F1 and Sp1, consequently leading to fully activation of E2F1/Sp1. Our findings provide a novel insight into understanding of specific function of BIR2 and BIR3 of XIAP in BC invasion, which will be highly significant for the design/synthesis of new BIR2/BIR3-based compounds for invasive BC treatment.

scholarly journals ABA-induced cytoplasmic translocation of COP1 enhances ROS accumulation through the HY5-ABI5 pathway to modulate seed germination

2021 ◽  
Author(s):  
Qing-Bin Chen ◽  
Wenjing Wang ◽  
Yue Zhang ◽  
Qidi Zhan ◽  
Kang Liu ◽  
...  
Keyword(s):  
Seed Germination ◽  
Target Genes ◽  
Seedling Survival ◽  
Signal Transduction Pathway ◽  
Negative Regulator ◽  
Protein Levels ◽  
Aba Signal Transduction ◽  
Ros Accumulation ◽  
Light Signals ◽  
Cytoplasmic Translocation

Seed germination is a physiological process regulated by multiple factors. Abscisic acid (ABA) can inhibit seed germination to improve seedling survival under conditions of abiotic stress, and this process is often regulated by light signals. Constitutive Photomorphogenic 1 (COP1) is an upstream core repressor of light signals, and is involved in several ABA responses. Here, we demonstrate that COP1 is a negative regulator of the ABA-mediated inhibition of seed germination. Disruption of COP1 enhanced Arabidopsis seed sensitivity to ABA and increased ROS levels. In seeds, ABA induced the translocation of COP1 to the cytoplasm, resulting in enhanced ABA-induced ROS levels. Genetic evidence indicated that HY5 and ABI5 act downstream of COP1 in the ABA-mediated inhibition of seed germination. ABA-induced COP1 cytoplasmic localization increased HY5 and ABI5 protein levels in the nucleus, leading to increased expression of ABI5 target genes and ROS levels in seeds. Together, our results reveal that ABA-induced cytoplasmic translocation of COP1 activates the HY5-ABI5 pathway to promote the expression of ABA-responsive genes and the accumulation of ROS during ABA-mediated inhibition of seed germination. These findings enhance the role of COP1 in the ABA signal transduction pathway.

scholarly journals Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for p63α Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell Tumorigenicity

2018 ◽  
Vol 38 (21) ◽  
Author(s):  
Xin Li ◽  
Zhongxian Tian ◽  
Honglei Jin ◽  
Jiheng Xu ◽  
Xiaohui Hua ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cyclin D1 ◽  
Gene Transcription ◽  
Mrna Stability ◽  
Rna Binding ◽  
D1 Protein ◽  
Protein Translation ◽  
The United States ◽  
Negative Regulator ◽  
Anchorage Independent Growth

ABSTRACTBladder cancer (BC) ranks as the sixth most common cancer in the United States and is the leading cause of death in patients with urinary malignancies. p63 is a member of the p53 family and is believed to function as a tumor suppressor in human BCs. Our most recent studies revealed a previously unknown function of the RING of XIAP in promoting microRNA 4295 (miR-4295) transcription, thereby reducing p63α protein translation and enhancing normal urothelial transformation, whereas p63α upregulates hsp70 transcription, subsequently activating the HSP70/Wasf3/Wave3/matrix metalloproteinase 9 (MMP-9) axis and promoting BC cell invasion via initiating the transcription factor E2F1. In this study, we found that p63α inhibited cyclin D1 protein expression, subsequently decreasing the ability of BC cell anchorage-independent growthin vitroand tumorigenicityin vivo. Mechanistic studies demonstrated that p63α expression is able to downregulate cyclin D1 gene transcription through attenuation of c-Myc mRNA stability. We further show that the reduction of miR-141-3p expression by p63α directly releases its inhibition of 3′ untranslated region (UTR) activity of AU-rich element RNA-binding factor 1 (AUF1) mRNA, thereby increasing AUF1 protein translation and further resulting in degradation of c-Myc mRNA, which, in turn, reduces cyclin D1 gene transcription and BC cell anchorage-independent growth. Collectively, our results demonstrate that p63α is a negative regulator of BC cell tumorigenic growth, a distinctly different function than its promotion of BC invasion, thus providing further new insight into the “two faces” of p63α in regulation of BC cell tumorigenic growth and progression/invasion.

scholarly journals XIAP Interaction with E2F1 and Sp1 via its BIR2 and BIR3 domains specific activated MMP2 to promote bladder cancer invasion

Oncogenesis ◽  
2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Jiheng Xu ◽  
Xiaohui Hua ◽  
Rui Yang ◽  
Honglei Jin ◽  
Jingxia Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Invasion ◽  
Feedback Loop ◽  
Ectopic Expression ◽  
Direct Interaction ◽  
Protein Translation ◽  
Negative Regulator ◽  
Cancer Cell Invasion ◽  
Design Synthesis ◽  
First Time

AbstractXIAP has generally been thought to function in bladder cancer. However, the potential function of structure-based function of XIAP in human BC invasion has not been well explored before. We show here that ectopic expression of the BIR domains of XIAP specifically resulted in MMP2 activation and cell invasion in XIAP-deleted BC cells, while Src was further defined as an XIAP downstream negative regulator for MMP2 activation and BC cell invasion. The inhibition of Src expression by the BIR domains was caused by attenuation of Src protein translation upon miR-203 upregulation; which was resulted from direct interaction of BIR2 and BIR3 with E2F1 and Sp1, respectively. The interaction of BIR2/BIR3 with E2F1/Sp1 unexpectedly occurred, which could be blocked by serum-induced XIAP translocation. Taken together, our studies, for the first time revealed that: (1) BIR2 and BIR3 domains of XIAP play their role in cancer cell invasion without affecting cell migration by specific activation of MMP2 in human BC cells; (2) by BIR2 interacting with E2F1 and BIR3 interacting with Sp1, XIAP initiates E2F1/Sp1 positive feedback loop-dependent transcription of miR-203, which in turn inhibits Src protein translation, further leading to MMP2-cleaved activation; (3) XIAP interaction with E2F1 and Sp1 is observed in the nucleus. Our findings provide novel insights into understanding the specific function of BIR2 and BIR3 of XIAP in BC invasion, which will be highly significant for the design/synthesis of new BIR2/BIR3-based compounds for invasive BC treatment.

Molecular and functional characterization of Brassica BREVIPEDICELLUS orthologs involved in inflorescence architectureThis paper is one of a selection of papers published in a Special Issue from the National Research Council of Canada – Plant Biotechnology Institute.

Botany ◽  
2009 ◽  
Vol 87 (6) ◽  
pp. 604-615 ◽  
Author(s):  
Tim Dumonceaux ◽  
Sathya Prakash Venglat ◽  
Kumuda Kushalappa ◽  
Gopalan Selvaraj ◽  
Raju Datla
Keyword(s):  
Developmental Process ◽  
Functional Characterization ◽  
Amino Acid Level ◽  
Ectopic Expression ◽  
National Research Council ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Inflorescence Architecture ◽  
Crop Species ◽  
Brassica Crop

The diversity of inflorescence architecture in angiosperms relates to attracting pollinators and allowing the effective dispersal of seeds. Molecular understanding of the genetic factors regulating inflorescence architecture from the model system of Arabidopsis could provide critical insights for addressing this developmental process/pathway in a closely related crop species like Brassica napus L. Towards this objective, we have isolated and characterized the orthologs of the homeobox gene BREVIPEDICELLUS (BP) in three Brassica species, B. napus (BnBP), Brassica rapa  L. (BrBP), and Brassica oleracea  L. (BoBP). These Brassica orthologs show a high degree of conservation at the nucleotide and amino acid level, including the homeodomain and the intron positions. The B. napus ortholog complemented the Arabidopsis bp null allele and overexpression of BnBP in B. napus transgenic lines resulted in altered leaf phenotypes. Together, these results suggest that Brassica BP genes are functional orthologs of Arabidopsis BP. Ectopic expression of AS2, a negative regulator of BP encoding a LOB domain transcription factor, in transgenic B. napus produced compact inflorescence architecture reminiscent of the loss-of-function bp mutant phenotype described previously in Arabidopsis. These results provide evidence in support of BP as a potential target gene for modifying inflorescence architecture in Brassica crop species.

scholarly journals Stress response in Entamoeba histolytica is associated with robust processing of tRNA to tRNA-halves

2021 ◽  
Author(s):  
Manu Sharma ◽  
Hanbang Zhang ◽  
Gretchen Ehrenkaufer ◽  
Upinder Singh
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Environmental Stress ◽  
Developmental Process ◽  
Protein Translation ◽  
Serum Starvation ◽  
Small Rna Sequencing ◽  
Cell Functions ◽  
Argonaute Proteins ◽  
Trna Halves

AbstracttRNA-derived fragments have been reported in many different organisms and have diverse cellular roles such as regulating gene expression, inhibiting protein translation, silencing transposable elements and modulating cell proliferation. In particular tRNA halves, a class of tRNA fragments produced by the cleavage of tRNAs in the anti-codon loop, have been widely reported to accumulate under stress and regulate translation in cells. Here we report the presence of tRNA-derived fragments in Entamoeba with tRNA halves being the most abundant. We further established that tRNA halves accumulate in the parasites upon different stress stimuli such as oxidative stress, heat shock, and serum starvation. We also observed differential expression of tRNA halves during developmental changes of trophozoite to cyst conversion with various tRNA halves accumulating during early encystation. In contrast to other systems, the stress response does not appear to be mediated by a few specific tRNA halves as multiple tRNAs appear to be processed during the various stresses. Furthermore, we identified some tRNA-derived fragments are associated with Entamoeba Argonaute proteins, EhAgo2-2, and EhAgo2-3, which have a preference for different tRNA-derived fragment species. Finally, we show that tRNA halves are packaged inside extracellular vesicles secreted by amoeba. The ubiquitous presence of tRNA-derived fragments, their association with the Argonaute proteins, and the accumulation of tRNA halves during multiple different stresses including encystation suggest a nuanced level of gene expression regulation mediated by different tRNA-derived fragments in Entamoeba.ImportancetRNA-derived fragments are small RNAs formed by the cleavage of tRNAs at specific positions. These have been reported in many organisms to modulate gene expression and thus regulate various cell functions. In the present study, we report for the first time the presence of tRNA-derived fragments in Entamoeba. tRNA-derived fragments were identified by bioinformatics analyses of small RNA sequencing datasets from the parasites and also confirmed experimentally. We found that tRNA halves accumulated in parasites exposed to environmental stress or during developmental process of encystation. We also found that shorter tRNA-derived fragments are bound to Entamoeba Argonaute proteins, indicating that they may have a potential role in the Argonaute-mediated RNA-interference pathway which mediates robust gene silencing in Entamoeba. Our results suggest that tRNA-derived fragments in Entamoeba have a possible role in regulating gene expression during environmental stress.

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