scholarly journals Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 88
Author(s):  
Yuichi Morozumi ◽  
Kazuhiro Shiozaki

Target of rapamycin complex 1 (TORC1), a serine/threonine-protein kinase complex highly conserved among eukaryotes, coordinates cellular growth and metabolism with environmental cues, including nutrients and growth factors. Aberrant TORC1 signaling is associated with cancers and various human diseases, and TORC1 also plays a key role in ageing and lifespan, urging current active research on the mechanisms of TORC1 regulation in a variety of model organisms. Identification and characterization of the RAG small GTPases as well as their regulators, many of which are highly conserved from yeast to humans, led to a series of breakthroughs in understanding the molecular bases of TORC1 regulation. Recruitment of mammalian TORC1 (mTORC1) by RAGs to lysosomal membranes is a key step for mTORC1 activation. Interestingly, the RAG GTPases in fission yeast are primarily responsible for attenuation of TORC1 activity on vacuoles, the yeast equivalent of lysosomes. In this review, we summarize our current knowledge about the functions of TORC1 regulators on yeast vacuoles, and illustrate the conserved and divergent mechanisms of TORC1 regulation between yeasts and mammals.

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuan Dai ◽  
Weijia Luo ◽  
Xiaojing Yue ◽  
Wencai Ma ◽  
Jing Wang ◽  
...  

Abstract The Rho family of GTPases consists of 20 members including RhoE. Here, we discover the existence of a short isoform of RhoE designated as RhoEα, the first Rho GTPase isoform generated from alternative translation. Translation of this new isoform is initiated from an alternative start site downstream of and in-frame with the coding region of the canonical RhoE. RhoEα exhibits a similar subcellular distribution while its protein stability is higher than RhoE. RhoEα contains binding capability to RhoE effectors ROCK1, p190RhoGAP and Syx. The distinct transcriptomes of cells with the expression of RhoE and RhoEα, respectively, are demonstrated. The data propose distinctive and overlapping biological functions of RhoEα compared to RhoE. In conclusion, this study reveals a new Rho GTPase isoform generated from alternative translation. The discovery provides a new scope of understanding the versatile functions of small GTPases and underlines the complexity and diverse roles of small GTPases.


Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 147 ◽  
Author(s):  
Cássio R. M. Souza ◽  
Wallace P. Bezerra ◽  
Janeusa T. Souto

Alkaloids are nitrogenous compounds with various biological activities. Alkaloids with anti-inflammatory activity are commonly found in terrestrial plants, but there are few records of the identification and characterization of the activity of these compounds in marine organisms such as fungi, bacteria, sponges, ascidians, and cnidarians. Seaweed are a source of several already elucidated bioactive compounds, but few studies have described and characterized the activity of seaweed alkaloids with anti-inflammatory properties. In this review, we have gathered the current knowledge about marine alkaloids with anti-inflammatory activity and suggest future perspectives for the study and bioprospecting of these compounds.


2003 ◽  
Vol 358 (1434) ◽  
pp. 1133-1140 ◽  
Author(s):  
C. Nathan Hancock ◽  
Katsuhiko Kondo ◽  
Brian Beecher ◽  
Bruce McClure

Plants have many ways to regulate the type of pollen that arrives on the stigma surface. Once there, further control mechanisms regulate compatibility. The latter controls are largely based on biochemical interactions that support compatible pollination and prevent incompatible matings. S–RNase–based self–incompatibility (SI) systems are the most phylogenetically widespread mechanisms for controlling pollination. Studies of Nicotiana establish a firm link between SI and unilateral interspecific incompatibility. Although implicated in both inter– and intraspecific compatibility, S–RNase operates through at least three distinct genetic mechanisms that differ in their dependence on non–S–RNase factors. Identification and characterization of these non–S–RNase factors is currently an area of active research. Searching for genetic and biochemical interactions with S–RNase can identify candidate non–S–RNase factors. HT–protein is one factor that is required for S –allele–specific pollen rejection in the Solanaceae. Major style arabinogalactan proteins such as TTS interact biochemically with S–RNase. These glycoproteins are known to interact with compatible pollen tubes and have long been suggested as possible recognition molecules. Their binding to S–RNase implies a link between stylar systems for compatibility and incompatibility. Thus, genetic and biochemical studies suggest a highly networked picture of pollen–pistil interactions.


Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 791-800 ◽  
Author(s):  
F. Wittwer ◽  
A. van der Straten ◽  
K. Keleman ◽  
B.J. Dickson ◽  
E. Hafen

Members of the AF4/FMR2 family of nuclear proteins are involved in human diseases such as acute lymphoblastic leukemia and mental retardation. Here we report the identification and characterization of the Drosophila lilliputian (lilli) gene, which encodes a nuclear protein related to mammalian AF4 and FMR2. Mutations in lilli suppress excessive neuronal differentiation in response to a constitutively active form of Raf in the eye. In the wild type, Lilli has a partially redundant function in the Ras/MAPK pathway in differentiation but it is essential for normal growth. Loss of Lilli function causes an autonomous reduction in cell size and partially suppresses the increased growth associated with loss of PTEN function. These results suggest that Lilli acts in parallel with the Ras/MAPK and the PI3K/PKB pathways in the control of cell identity and cellular growth.


2009 ◽  
Vol 191 (18) ◽  
pp. 5622-5627 ◽  
Author(s):  
Chaitanya Jain

ABSTRACT RNases are involved in critical aspects of RNA metabolism in all organisms. Two classes of RNases that digest RNA from an end (exo-RNases) are known: RNases that use water as a nucleophile to catalyze RNA degradation (hydrolytic RNases) and RNases that use inorganic phosphate (phosphorolytic RNases). It has been shown previously that the absence of the two known Escherichia coli phosphorolytic RNases, polynucleotide phosphorylase and RNase PH, leads to marked growth and ribosome assembly defects. To investigate the basis for these defects, a screen for growth suppressors was performed. The majority of suppressor mutations were found to lie within nsrR, which encodes a nitric oxide (NO)-sensitive transcriptional repressor. Further analysis showed that the suppressors function not by inactivating nsrR but by causing overexpression of a downstream gene that encodes a hydrolytic RNase, RNase R. Additional studies revealed that overexpression of another hydrolytic RNase, RNase II, similarly suppressed the growth defects. These results suggest that the requirement for phosphorolytic RNases for robust cellular growth and efficient ribosome assembly can be bypassed by increased expression of hydrolytic RNases.


2001 ◽  
Vol 8 (2) ◽  
pp. 370-375 ◽  
Author(s):  
Robert Bals ◽  
Christiane Lang ◽  
Daniel J. Weiner ◽  
Claus Vogelmeier ◽  
Ulrich Welsch ◽  
...  

ABSTRACT One component of host defense at mucosal surfaces appears to be epithelium-derived antimicrobial peptides. Molecules of the defensin and cathelicidin families have been studied in several species, including human and mouse. We describe in this report the identification and characterization of rhesus monkey homologues of human mucosal antimicrobial peptides. Using reverse transcriptase PCR methodology, we cloned the cDNAs of rhesus monkey β-defensin 1 and 2 (rhBD-1 and rhBD-2) and rhesus monkey LL-37/CAP-18 (rhLL-37/rhCAP-18). The predicted amino acid sequences showed a high degree of homology to the human molecules. The expression of the monkey antimicrobial peptides was analyzed using immunohistochemistry with three polyclonal antibodies to the human molecules. As in humans, rhesus monkey antimicrobial peptides are expressed in epithelia of various organs. The present study demonstrates that β-defensins and cathelicidins of rhesus monkeys are close homologues to the human molecules and indicate that nonhuman primates represent valid model organisms to study innate immune functions.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 71
Author(s):  
Wai Hoong Chang ◽  
Alvina G. Lai

The homeodomain-containing proteins are an important group of transcription factors found in most eukaryotes including animals, plants and fungi. Homeobox genes are responsible for a wide range of critical developmental and physiological processes, ranging from embryonic development, innate immune homeostasis to whole-body regeneration. With continued fascination on this key class of proteins by developmental and evolutionary biologists, multiple efforts have thus far focused on the identification and characterization of homeobox orthologs from key model organisms in attempts to infer their evolutionary origin and how this underpins the evolution of complex body plans. Despite their importance, the genetic complement of homeobox genes has yet been described in one of the most valuable groups of animals representing economically important food crops. With crustacean aquaculture being a growing industry worldwide, it is clear that systematic and cross-species identification of crustacean homeobox orthologs is necessary in order to harness this genetic circuitry for the improvement of aquaculture sustainability. Using publicly available transcriptome data sets, we identified a total of 4183 putative homeobox genes from 120 crustacean species that include food crop species, such as lobsters, shrimps, crayfish and crabs. Additionally, we identified 717 homeobox orthologs from 6 other non-crustacean arthropods, which include the scorpion, deer tick, mosquitoes and centipede. This high confidence set of homeobox genes will now serve as a key resource to the broader community for future functional and comparative genomics studies.


Author(s):  
Anna Cazzola ◽  
Giovanni Cazzaniga ◽  
Andrea Biondi ◽  
Raffaella Meneveri ◽  
Silvia Brunelli ◽  
...  

Several lines of evidence suggest that childhood leukemia, the most common cancer in young age, originates during in utero development. However, our knowledge of the cellular origin of this large and heterogeneous group of malignancies is still incomplete. The identification and characterization of their cell of origin is of crucial importance in order to define the processes that initiate and sustain disease progression, to refine faithful animal models and to identify novel therapeutic approaches. During embryogenesis, hematopoiesis takes place at different anatomical sites in sequential waves, and occurs in both a hematopoietic stem cell (HSC)-dependent and a HSC-independent fashion. Despite the recently described relevance and complexity of HSC-independent hematopoiesis, few studies have so far investigated its potential involvement in leukemogenesis. Here, we review the current knowledge on prenatal origin of leukemias in the context of recent insights in developmental hematopoiesis.


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