scholarly journals Oncogenic kinases and perturbations in protein synthesis machinery and energetics in neoplasia

2019 ◽  
Vol 62 (2) ◽  
pp. R83-R103 ◽  
Author(s):  
Oro Uchenunu ◽  
Michael Pollak ◽  
Ivan Topisirovic ◽  
Laura Hulea

Notwithstanding that metabolic perturbations and dysregulated protein synthesis are salient features of cancer, the mechanism underlying coordination of cellular energy balance with mRNA translation (which is the most energy consuming process in the cell) is poorly understood. In this review, we focus on recently emerging insights in the molecular underpinnings of the cross-talk between oncogenic kinases, translational apparatus and cellular energy metabolism. In particular, we focus on the central signaling nodes that regulate these processes (e.g. the mechanistic/mammalian target of rapamycin MTOR) and the potential implications of these findings on improving the anti-neoplastic efficacy of oncogenic kinase inhibitors.

2021 ◽  
Author(s):  
Anish Das ◽  
Tong Liu ◽  
Hong Li ◽  
Seema Husain

AbstractRNA-binding proteins are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long arrays of unrelated genes. In this report, we present a systematic analysis of an essential RNA-binding protein, RBP42, in the mammalian-infective slender bloodstream form of African trypanosome, and we show that RBP42 is a key regulator of parasite’s central carbon and energy metabolism. Using individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to identify genome-wide RBP42-RNA interactions, we show that RBP42 preferentially binds within the coding region of mRNAs encoding core metabolic enzymes. Using global quantitative transcriptomic and proteomic analyses, we also show that loss of RBP42 reduces the abundance of target mRNA-encoded proteins, but not target mRNA, suggesting a plausible role of RBP42 as a positive regulator of target mRNA translation. Analysis reveals significant changes in central carbon metabolic intermediates following loss of RBP42, further supporting its critical role in cellular energy metabolism.


2017 ◽  
Vol 233 (4) ◽  
pp. 3465-3475 ◽  
Author(s):  
Weinan Zhou ◽  
Deepti Ramachandran ◽  
Abdelhak Mansouri ◽  
Megan J. Dailey

2016 ◽  
Vol 5 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Torsten Schröder ◽  
David Kucharczyk ◽  
Florian Bär ◽  
René Pagel ◽  
Stefanie Derer ◽  
...  

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262613
Author(s):  
Clara Dreyling ◽  
Martin Hasselmann

The cellular energy metabolism is one of the most conserved processes, as it is present in all living organisms. Mitochondria are providing the eukaryotic cell with energy and thus their genome and gene expression has been of broad interest for a long time. Mitochondrial gene expression changes under different conditions and is regulated by genes encoded in the nucleus of the cell. In this context, little is known about non-model organisms and we provide the first large-scaled gene expression analysis of mitochondrial-linked genes in laying hens. We analysed 28 mitochondrial and nuclear genes in 100 individuals in the context of five life-stages and strain differences among five tissues. Our study showed that mitochondrial gene expression increases during the productive life span, and reacts tissue and strain specific. In addition, the strains react different to potential increased oxidative stress, resulting from the increase in mitochondrial gene expression. The results suggest that the cellular energy metabolism as part of a complex regulatory system is strongly affected by the productive life span in laying hens and thus partly comparable to model organisms. This study provides a starting point for further analyses in this field on non-model organisms, especially in laying-hens.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Laimonas Kelbauskas ◽  
Shashaanka P. Ashili ◽  
Kristen B. Lee ◽  
Haixin Zhu ◽  
Yanqing Tian ◽  
...  

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