The role of Rsp5 ubiquitin ligase in regulation of diverse processes in yeast cells.

2008 ◽  
Vol 55 (4) ◽  
pp. 649-662 ◽  
Author(s):  
Paweł Kaliszewski ◽  
Teresa Zoładek
Keyword(s):  
Fatty Acid ◽  
Ubiquitin Ligase ◽  
Intracellular Trafficking ◽  
Phospholipid Composition ◽  
Multivesicular Body ◽  
Yeast Cells ◽  
Sterol Synthesis ◽  
Cellular Processes ◽  
Number Of Publications

Rsp5 is a conserved ubiquitin ligase involved in regulation of numerous cellular processes. A growing number of publications describing new functions of the ligase have appeared in recent years. Rsp5 was shown to be involved in the control of intracellular trafficking of proteins via endocytosis and multivesicular body sorting. Moreover, nuclear functions of Rsp5 in response to various stresses have been discovered. Rsp5 is also involved in the regulation of unsaturated fatty acid and sterol synthesis and phospholipid composition. Here, an overview of Rsp5 functions with emphasis on its involvement in the regulation of lipid biosynthesis will be presented.

scholarly journals Non–SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function

2011 ◽  
Vol 22 (9) ◽  
pp. 1575-1584 ◽  
Author(s):  
Yuan Liu ◽  
Kunio Nakatsukasa ◽  
Michiko Kotera ◽  
Akira Kanada ◽  
Takashi Nishimura ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Intracellular Trafficking ◽  
Intracellular Transport ◽  
Yeast Cells ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
F Box Protein

Skp1/Cul1/F-box (SCF)–type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non–SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5′-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins therefore remains largely elusive. Here we analyze the role of a previously uncharacterized non–SCF-type F-box protein, Roy1/Ymr258c, in cell growth and intracellular transport in Saccharomyces cerevisiae. Roy1 binds to Ypt52 under physiological conditions, and Skp1 is indispensable for the association of Roy1 with Ypt52. The vps21Δ yeast cells exhibit severe deficiencies in cell growth and intracellular trafficking, whereas simultaneous deletion of roy1 alleviates the defects caused by deletion of vps21. However, additional disruption of ypt52 in roy1Δvps21Δ cells largely suppresses the cell growth and trafficking observed in roy1Δvps21Δ cells. We demonstrate that Roy1 interacts with guanosine 5′-diphosphate–bound and nucleotide-free Ypt52 and thereby inhibits the formation of guanosine 5′-triphosphate–bound, active Ypt52. These results thus indicate that Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52.

scholarly journals Homocysteine as a Risk Factor for Atherosclerosis: Is Its Conversion toS-Adenosyl-L-Homocysteine the Key to Deregulated Lipid Metabolism?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Oksana Tehlivets
Keyword(s):  
Risk Factor ◽  
Lipid Metabolism ◽  
Mammalian Cells ◽  
Yeast Cells ◽  
Sterol Synthesis ◽  
Unfolded Protein ◽  
Strong Product ◽  
The Unfolded Protein Response ◽  
Protein Response

Homocysteine (Hcy) has been recognized for the past five decades as a risk factor for atherosclerosis. However, the role of Hcy in the pathological changes associated with atherosclerosis as well as the pathological mechanisms triggered by Hcy accumulation is poorly understood. Due to the reversal of the physiological direction of the reaction catalyzed byS-adenosyl-L-homocysteine hydrolase Hcy accumulation leads to the synthesis ofS-adenosyl-L-homocysteine (AdoHcy). AdoHcy is a strong product inhibitor ofS-adenosyl-L-methionine (AdoMet)-dependent methyltransferases, and to date more than 50 AdoMet-dependent methyltransferases that methylate a broad spectrum of cellular compounds including nucleic acids, proteins and lipids have been identified. Phospholipid methylation is the major consumer of AdoMet, both in mammals and in yeast. AdoHcy accumulation induced either by Hcy supplementation or due toS-adenosyl-L-homocysteine hydrolase deficiency results in inhibition of phospholipid methylation in yeast. Moreover, yeast cells accumulating AdoHcy also massively accumulate triacylglycerols (TAG). Similarly, Hcy supplementation was shown to lead to increased TAG and sterol synthesis as well as to the induction of the unfolded protein response (UPR) in mammalian cells. In this review a model of deregulation of lipid metabolism in response to accumulation of AdoHcy in Hcy-associated pathology is proposed.

scholarly journals The role of SCF ubiquitin-ligase complex at the beginning of life

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cellular Proteins ◽  
Cell Cycle Regulators ◽  
Signal Transducers ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin Ligase Complex ◽  
Scf Ubiquitin Ligase

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.

scholarly journals A dual role for K63-linked ubiquitin chains in multivesicular body biogenesis and cargo sorting

2012 ◽  
Vol 23 (11) ◽  
pp. 2170-2183 ◽  
Author(s):  
Zoi Erpapazoglou ◽  
Manel Dhaoui ◽  
Marina Pantazopoulou ◽  
Francesca Giordano ◽  
Muriel Mari ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Transmembrane Proteins ◽  
Multivesicular Body ◽  
Dual Role ◽  
Yeast Cells ◽  
Endosomal Sorting ◽  
Binding Domains ◽  
Double Function ◽  
Ubiquitin Binding ◽  
Cargo Sorting

In yeast, the sorting of transmembrane proteins into the multivesicular body (MVB) internal vesicles requires their ubiquitylation by the ubiquitin ligase Rsp5. This allows their recognition by the ubiquitin-binding domains (UBDs) of several endosomal sorting complex required for transport (ESCRT) subunits. K63-linked ubiquitin (K63Ub) chains decorate several MVB cargoes, and accordingly we show that they localize prominently to the class E compartment, which accumulates ubiquitylated cargoes in cells lacking ESCRT components. Conversely, yeast cells unable to generate K63Ub chains displayed MVB sorting defects. These properties are conserved among eukaryotes, as the mammalian melanosomal MVB cargo MART-1 is modified by K63Ub chains and partly missorted when the genesis of these chains is inhibited. We show that all yeast UBD-containing ESCRT proteins undergo ubiquitylation and deubiquitylation, some being modified through the opposing activities of Rsp5 and the ubiquitin isopeptidase Ubp2, which are known to assemble and disassemble preferentially K63Ub chains, respectively. A failure to generate K63Ub chains in yeast leads to an MVB ultrastructure alteration. Our work thus unravels a double function of K63Ub chains in cargo sorting and MVB biogenesis.

scholarly journals Caenorhabditis elegansF09E10.3 Encodes a Putative 3-Oxoacyl-Thioester Reductase of Mitochondrial Type 2 Fatty Acid Synthase FASII that Is Functional in Yeast

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Aner Gurvitz
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Reductase Activity ◽  
Carbon Sources ◽  
Yeast Cells ◽  
C Elegans ◽  
Animal Physiology ◽  
Mutant Cells

Caenorhabditis elegansF09E10.3 (dhs-25) was identified as encoding a 3-oxoacyl-thioester reductase, potentially of the mitochondrial type 2 fatty acid synthase (FASII) system. Mitochondrial FASII is a relatively recent discovery in metazoans, and the relevance of this process to animal physiology has not been elucidated. A good animal model to study the role of FASII is the nematodeC. elegans. However, the components of nematode mitochondrial FASII have hitherto evaded positive identification. The nematode F09E10.3 protein was ectopically expressed without an additional mitochondrial targeting sequence inSaccharomyces cerevisiaemutant cells lacking the homologous mitochondrial FASII enzyme 3-oxoacyl-ACP reductase Oar1p. These yeastoar1Δmutants are unable to respire, grow on nonfermentable carbon sources, or synthesize sufficient levels of lipoic acid. Mutant yeast cells producing a full-length mitochondrial F09E10.3 protein containedNAD+-dependent 3-oxoacyl-thioester reductase activity and resembled the corresponding mutant overexpressing native Oar1p for the above-mentioned phenotype characteristics. This is the first identification of a metazoan 3-oxoacyl-thioester reductase (see Note Added in Proof).

Deubiquitylating enzymes in receptor endocytosis and trafficking

2016 ◽  
Vol 473 (24) ◽  
pp. 4507-4525 ◽  
Author(s):  
Aidan P. McCann ◽  
Christopher J. Scott ◽  
Sandra Van Schaeybroeck ◽  
James F. Burrows
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Therapeutic Targets ◽  
Multivesicular Body ◽  
Lysosomal Degradation ◽  
Transmembrane Receptors ◽  
Receptor Endocytosis ◽  
Cellular Processes

In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane. In this review, we will discuss in detail what is currently known about the role of DUBs in regulating the endocytosis of various transmembrane receptors and ion channels. We will also expand upon the role DUBs play in receptor sorting at the multivesicular body to determine whether a receptor is recycled or trafficked to the lysosome for degradation. Finally, we will briefly discuss how the DUBs implicated in these processes may contribute to the pathogenesis of a range of diseases, and thus the potential these have as therapeutic targets.

scholarly journals The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 422 ◽  
Author(s):  
Laura Picas ◽  
Frederique Gaits-Iacovoni ◽  
Bruno Goud
Keyword(s):  
Signal Transduction ◽  
Intracellular Trafficking ◽  
Recent Observation ◽  
Metabolizing Enzymes ◽  
Master Regulators ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Cytoskeleton Dynamics ◽  
Protein Modules

Phosphoinositides are master regulators of multiple cellular processes: from vesicular trafficking to signaling, cytoskeleton dynamics, and cell growth. They are synthesized by the spatiotemporal regulated activity of phosphoinositide-metabolizing enzymes. The recent observation that some protein modules are able to cluster phosphoinositides suggests that alternative or complementary mechanisms might operate to stabilize the different phosphoinositide pools within cellular compartments. Herein, we discuss the different known and potential molecular players that are prone to engage phosphoinositide clustering and elaborate on how such a mechanism might take part in the regulation of intracellular trafficking and signal transduction.

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