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Using a high-throughput kinase activity mapping platform, Ruiz-Saenz A et al identified that Proto-oncogene tyrosine-protein kinase (SRC) kinases are systematically activated in BRAF(V600E) CRC following targeted inhibition of BRAF and EGFR. Drug-drug synthetic lethality to combat cancer: From bench to bedside However, melanoma cells express little EGFR; therefore, BRAF inhibitors did not stimulate EGFR activation. [Extracted from the article]

Interestingly, only critically ill COVID-19 and hospitalized COVID-19 were found to have a suggestive causal effect on gastric cancer, while the causal effects of COVID-19 on other digestive tract cancers disappeared (Figure 1). Previous studies have shown that patients suffering from cancer are more susceptible to COVID-19 and more severe.[[4]] Therefore, it is worth addressing whether COVID-19 has causal effects on cancer or cancer causes COVID-19. COVID-19 has causal effects on cancer risk?. [Extracted from the article]

Summary: Cyanobacteria have an inherited advantage in phosphonate phytoremediation. However, studies on phosphonate metabolism in cyanobacteria are rare and mostly focus on physiology and ecology. Here, C‐P lyase gene cluster regulation in an undomesticated thermophilic Synechococcus OS‐B′ was examined in Synechocystis sp. PCC6803, a unicellular cyanobacterial model. Phylogenetic and cluster synteny analysis of C‐P lyase genes revealed a closer relationship between Syn OS‐B′ and Thermus thermophilus, than with other cyanobacteria. Pho boxes were identified in the 5′‐end‐flanking region of the C‐P lyase gene cluster, through which the downstream gene expression was regulated in a phosphate concentration‐dependent manner. Unexpectedly, the phosphate concentration that thoroughly inhibited Pho boxes was almost two orders of magnitude higher than that of any natural or anthropogenic wastewater reported so far. The Pho boxes mediated regulation was achieved through the Pho regulon two‐component system, and the absence of either SphS or SphR ablated the cell's ability to sense ambient phosphate changes. The three tandems of Pho boxes maintained inequivalent roles, of which the third tandem was not essential; however, it played a role in adjusting Pho boxes response in both positive and negative manner under phosphorus limitation. [ABSTRACT FROM AUTHOR]

Summary: Forward and reverse genetics using the model legumes Lotus japonicus and Medicago truncatula have been instrumental in identifying the essential genes governing legume–rhizobia symbiosis. However, little information is known about the effects of intraspecific variation on symbiotic signalling.Here, we use quantitative trait locus sequencing (QTL‐seq) to investigate the genetic basis of the differentiated phenotypic responses shown by the Lotus accessions Gifu and MG20 to inoculation with the Mesorhizobium loti exoU mutant that produces truncated exopolysaccharides.We identified through genetic complementation the Pxy gene as a component of this differential exoU response. Lotus Pxy encodes a leucine‐rich repeat receptor‐like kinase similar to Arabidopsis thaliana PXY, which regulates stem vascular development. We show that Lotus pxy insertion mutants displayed defects in root and stem vascular organisation, as well as lateral root and nodule formation.Our work links Pxy to de novo organogenesis in the root, highlights the genetic overlap between regulation of lateral root and nodule formation, and demonstrates that natural variation in Pxy affects nodulation signalling. [ABSTRACT FROM AUTHOR]

Summary: Protein quality control pathways require AAA+ proteases, such as Clp and Lon. Lon protease maintains UmuD, an important component of the error‐prone DNA repair polymerase (Pol V), at very low levels in E. coli. Most members of the phylum Cyanobacteria lack Lon (including the model cyanobacterium, Synechocystis sp. PCC6803), so maintenance of UmuD at low levels must employ different proteases. We demonstrate that the first 19 residues from the N‐terminus of UmuD (Sug1‐19) fused to a reporter protein are adequate to trigger complete proteolysis and that mutation of a single leucine residue (L6) to aspartic acid inhibits proteolysis. This process appears to follow the N‐end rule and is mediated by ClpA/P protease and the ClpS adaptor. Additionally, mutations of arginine residues in the Sug1‐19 tag suggest that the ClpX/P pathway also plays a role in proteolysis. We propose that there is a dual degron at the N‐terminus of the UmuD protein in Synechocystis sp. PCC6803, which is distinct from the degron required for degradation of UmuD in E. coli. The use of two proteolysis pathways to tune levels of UmuD might reflect how a photosynthetic organism responds to multiple environmental stressors. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are highly conserved proteins, which are expressed at low levels under normal conditions, but significantly induced in response to cellular stresses. As molecular chaperones, HSPs play crucial roles in protein homeostasis, apoptosis, invasion and cellular signaling transduction. The induction of HSPs is an important part of heat shock response, which could help cancer cells to adapt to stress conditions. Because of the constant stress condition in tumor microenvironment, HSPs overexpression is widely reported in many human cancers. In light of the significance of HSPs for cancer cells to survive and obtain invasive phenotype under stress condition, HSPs are often associated with poor prognosis and treatment resistance in many types of human cancers. It has been described that upregulation of HSPs may serve as diagnostic and prognostic markers in hepatocellular carcinoma (HCC). Targeting HSPs with specific inhibitor alone or in combination with chemotherapy regimens holds promise for the improvement of outcomes for HCC patients. In this review, we summarize the expression profiles, functions and molecular mechanisms of HSPs (HSP27, HSP70 and HSP90) as well as a HSP-like protein (clusterin) in HCC. In addition, we address progression and challenges in targeting these HSPs as novel therapeutic strategies in HCC. [ABSTRACT FROM AUTHOR]