SUMO/sentrin: protein modifiers regulating important cellular functions

1999 ◽  
Vol 77 (4) ◽  
pp. 299-309 ◽  
Author(s):  
Carole Kretz-Remy ◽  
Robert M Tanguay
Keyword(s):  
Subcellular Localization ◽  
Protein Modification ◽  
Protein Transport ◽  
Protein Localization ◽  
Cellular Functions ◽  
Nf Kappa B ◽  
Sumo Conjugation ◽  
Protein Functions ◽  
Specific Proteins ◽  
Substrate Proteins

Regulation of protein functions can be achieved by posttranslational protein modifications. One of the most studied modifications has been conjugation to ubiquitin, which mainly targets substrate proteins for degradation by the 26 S proteasome. Recently, SUMO/sentrin, a ubiquitin-like protein has been characterized. This evolutionary conserved protein is conjugated to specific proteins in a way similar, but not identical, to ubiquitin and seems also to be involved in the regulation of protein localization or function. An increasing number of SUMO/sentrin substrates are currently described. We focus here on three major substrates of modification by SUMO: RanGAP1, PML, and I(kappa)B(alpha) proteins. These different examples illustrate how SUMO conjugation may be involved in the control of the level of critical proteins within the cell or in the modulation of subcellular localization and nucleocytoplasmic trafficking.Key words: protein modification, NF-(kappa)B, I(kappa)B, protein transport, nucleus, RanGAP1, PML.

Role of O-Linked N-acetylglucosamine (O-GlcNAc) Protein Modification in Cellular (Patho)Physiology

2020 ◽  
Author(s):  
John C. Chatham ◽  
Jianhua Zhang ◽  
Adam Raymond Wende
Keyword(s):  
Chromatin Remodeling ◽  
Protein Modification ◽  
Protein Localization ◽  
Cellular Functions ◽  
Secretory Pathways ◽  
Cellular Physiology ◽  
Cytoplasmic Proteins ◽  
Wide Range ◽  
Glcnac Transferase

In the mid 1980s, the identification of serine and threonine residues on nuclear and cytoplasmic proteins modified by an O-linkage by a N-acetylglucosamine moiety (O-GlcNAc) overturned the widely held assumption that glycosylation only occurred in the endoplasmic reticulum, Golgi apparatus, and secretory pathways. In contrast to traditional glycosylation, the O-GlcNAc modification does not lead to complex branched glycan structures and is rapidly cycled on and off proteins by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Since its discovery O-GlcNAcylation has been shown to contribute to numerous cellular functions including signaling, protein localization and stability, transcription, chromatin remodeling, mitochondrial function, and cell survival. Dysregulation in O-GlcNAc cycling has been implicated in the progression of a wide range of diseases such as diabetes, diabetic complications, cancer, cardiovascular, and neurodegenerative diseases. This review will outline our current understanding of the processes involved in regulating O-GlcNAc turnover, the role of O-GlcNAcylation in regulating cellular physiology, and how dysregulation in O-GlcNAc cycling contributes to pathophysiological processes.

scholarly journals Compartmental organization of Golgi-specific protein modification and vacuolar protein sorting events defined in a yeast sec18 (NSF) mutant.

1991 ◽  
Vol 114 (2) ◽  
pp. 207-218 ◽  
Author(s):  
T R Graham ◽  
S D Emr
Keyword(s):  
Golgi Complex ◽  
Protein Modification ◽  
Secretory Pathway ◽  
Protein Transport ◽  
Temperature Shift ◽  
Specific Protein ◽  
Carboxypeptidase Y ◽  
Protein Functions ◽  
Dependent Transport ◽  
Vacuolar Protein

The sec18 and sec23 secretory mutants of Saccharomyces cerevisiae have previously been shown to exhibit temperature-conditional defects in protein transport from the ER to the Golgi complex (Novick, P., S. Ferro, and R. Schekman, 1981. Cell. 25:461-469). We have found that the Sec18 and Sec23 protein functions are rapidly inactivated upon shifting mutant cells to the nonpermissive temperature (less than 1 min). This has permitted an analysis of the potential role these SEC gene products play in transport events distal to the ER. The sec-dependent transport of alpha-factor (alpha f) and carboxypeptidase Y (CPY) biosynthetic intermediates present throughout the secretory pathway was monitored in temperature shift experiments. We found that Sec18p/NSF function was required sequentially for protein transport from the ER to the Golgi complex, through multiple Golgi compartments and from the Golgi complex to the cell surface. In contrast, Sec23p function was required in the Golgi complex, but only for transport of alpha f out of an early compartment. Together, these studies define at least three functionally distinct Golgi compartments in yeast. From cis to trans these compartments contain: (a) An alpha 1----6 mannosyltransferase; (b) an alpha 1----3 mannosyltransferase; and (c) the Kex2 endopeptidase. Surprisingly, we also found that a pool of Golgi-modified CPY (p2 CPY) located in a compartment distal to the alpha 1----3 mannosyltransferase does not require Sec18p function for final delivery to the vacuole. This compartment appears to be equivalent to the Kex2 compartment as we show that a novel vacuolar CPY-alpha f-invertase fusion protein undergoes efficient Kex2-dependent cleavage resulting in the secretion of invertase. We propose that this Kex2 compartment is the site in which vacuolar proteins are sorted from proteins destined to be secreted.

scholarly journals SUMOylation and calcium signalling: potential roles in the brain and beyond

2017 ◽  
Vol 1 (3) ◽  
Author(s):  
Leticia Coelho-Silva ◽  
Gary J. Stephens ◽  
Helena Cimarosti
Keyword(s):  
Protein Modification ◽  
Calcium Signalling ◽  
Cellular Functions ◽  
Normal Functioning ◽  
Sumo Conjugation ◽  
The Central Nervous System ◽  
Cardiac System ◽  
And Function ◽  
The Brain ◽  
Ca2 Channels

Small ubiquitin-like modifier (SUMO) conjugation (or SUMOylation) is a post-translational protein modification implicated in alterations to protein expression, localization and function. Despite a number of nuclear roles for SUMO being well characterized, this process has only started to be explored in relation to membrane proteins, such as ion channels. Calcium ion (Ca2+) signalling is crucial for the normal functioning of cells and is also involved in the pathophysiological mechanisms underlying relevant neurological and cardiovascular diseases. Intracellular Ca2+ levels are tightly regulated; at rest, most Ca2+ is retained in organelles, such as the sarcoplasmic reticulum, or in the extracellular space, whereas depolarization triggers a series of events leading to Ca2+ entry, followed by extrusion and reuptake. The mechanisms that maintain Ca2+ homoeostasis are candidates for modulation at the post-translational level. Here, we review the effects of protein SUMOylation, including Ca2+ channels, their proteome and other proteins associated with Ca2+ signalling, on vital cellular functions, such as neurotransmission within the central nervous system (CNS) and in additional systems, most prominently here, in the cardiac system.

Protein transport : bioinformatics methods for understanding protein subcellular localization

2018 ◽  
Author(s):  
◽  
Ning Zhang
Keyword(s):  
Machine Learning ◽  
Subcellular Localization ◽  
Protein Transport ◽  
Protein Localization ◽  
Mitochondrial Protein ◽  
Computational Prediction ◽  
Protein Subcellular Localization ◽  
Learning Methods ◽  
Web Resource ◽  
Machine Learning Methods

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Eukaryotic cells contain diverse subcellular organelles. These organelles form distinct functional cellular compartments where different biological processes and functions are carried out. The accurate translocation of a protein is crucial to establish and maintain cellular organization and function. Newly synthesized proteins are transported to different cellular components with the assistance of protein transport machineries and complex targeting signals. Mis-localization of proteins is often associated with metabolic disorders and diseases. Compared with experimental methods, computational prediction of protein localization, utilizing different machine learning methods, provides an efficient and effective way for studying the protein subcellular localization on the whole-proteome level. Here, we present in this dissertation the bioinformatics methods for studying protein subcellular localization. We reviewed the studies of protein subcellular transport and machine learning methods in bioinformatics, presented our work on mitochondrial protein targeting prediction in plants, summarized the ongoing development of a web-resource for protein subcellular localization, and discussed the future work and development.

scholarly journals Proteomic Analysis of the Arabidopsis Nucleolus Suggests Novel Nucleolar Functions

2005 ◽  
Vol 16 (1) ◽  
pp. 260-269 ◽  
Author(s):  
Alison F. Pendle ◽  
Gillian P. Clark ◽  
Reinier Boon ◽  
Dominika Lewandowska ◽  
Yun Wah Lam ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Ribosome Biogenesis ◽  
Protein Localization ◽  
Mrna Export ◽  
Exon Junction Complex ◽  
Unexpected Finding ◽  
Cellular Functions ◽  
Nonsense Mediated Decay ◽  
Wide Range ◽  
Specific Proteins

The eukaryotic nucleolus is involved in ribosome biogenesis and a wide range of other RNA metabolism and cellular functions. An important step in the functional analysis of the nucleolus is to determine the complement of proteins of this nuclear compartment. Here, we describe the first proteomic analysis of plant (Arabidopsis thaliana) nucleoli, in which we have identified 217 proteins. This allows a direct comparison of the proteomes of an important nuclear structure between two widely divergent species: human and Arabidopsis. The comparison identified many common proteins, plant-specific proteins, proteins of unknown function found in both proteomes, and proteins that were nucleolar in plants but nonnucleolar in human. Seventy-two proteins were expressed as GFP fusions and 87% showed nucleolar or nucleolar-associated localization. In a striking and unexpected finding, we have identified six components of the postsplicing exon-junction complex (EJC) involved in mRNA export and nonsense-mediated decay (NMD)/mRNA surveillance. This association was confirmed by GFP-fusion protein localization. These results raise the possibility that in plants, nucleoli may have additional functions in mRNA export or surveillance.

scholarly journals Influence of Subcellular Localization and Functional State on Protein Turnover

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1747
Author(s):  
Roya Yousefi ◽  
Kristina Jevdokimenko ◽  
Verena Kluever ◽  
David Pacheu-Grau ◽  
Eugenio F. Fornasiero
Keyword(s):  
Subcellular Localization ◽  
Functional State ◽  
Protein Turnover ◽  
Protein Localization ◽  
Small Gtpase ◽  
Turnover Rates ◽  
Cellular Behavior ◽  
Two Factors ◽  
Brain Creatine Kinase ◽  
Selection Of

Protein homeostasis is an equilibrium of paramount importance that maintains cellular performance by preserving an efficient proteome. This equilibrium avoids the accumulation of potentially toxic proteins, which could lead to cellular stress and death. While the regulators of proteostasis are the machineries controlling protein production, folding and degradation, several other factors can influence this process. Here, we have considered two factors influencing protein turnover: the subcellular localization of a protein and its functional state. For this purpose, we used an imaging approach based on the pulse-labeling of 17 representative SNAP-tag constructs for measuring protein lifetimes. With this approach, we obtained precise measurements of protein turnover rates in several subcellular compartments. We also tested a selection of mutants modulating the function of three extensively studied proteins, the Ca2+ sensor calmodulin, the small GTPase Rab5a and the brain creatine kinase (CKB). Finally, we followed up on the increased lifetime observed for the constitutively active Rab5a (Q79L), and we found that its stabilization correlates with enlarged endosomes and increased interaction with membranes. Overall, our data reveal that both changes in protein localization and functional state are key modulators of protein turnover, and protein lifetime fluctuations can be considered to infer changes in cellular behavior.

scholarly journals The AAA+ ATPase p97, a cellular multitool

2017 ◽  
Vol 474 (17) ◽  
pp. 2953-2976 ◽  
Author(s):  
Lasse Stach ◽  
Paul S. Freemont
Keyword(s):  
Atp Hydrolysis ◽  
Current Status ◽  
Cellular Functions ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Proteotoxic Stress ◽  
Binding Domains ◽  
Wide Range ◽  
Aaa Atpases ◽  
Substrate Proteins

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy.

scholarly journals Proteomic Analysis of Capacitated and Non-Capacitated Spermatozoa of Yanbian Yellow Cattle

2020 ◽  
Author(s):  
Xuan Chen ◽  
Zuochen Li ◽  
Yanqiu Lv ◽  
Yichao Xu ◽  
Mimi Cheng ◽  
...  
Keyword(s):  
Protein Transport ◽  
Expression Level ◽  
Molecular Processes ◽  
Proteomics Data ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Go Enrichment ◽  
Yellow Cattle ◽  
Specific Proteins ◽  
The Difference

Abstract Background: Sperm capacitation is a process which occurs prior to fertilization, and is essential for producing high-quality living embryos. The main purpose of this study was to explore the difference of proteomics between capacitated and non-capacitated sperm of Yanbian yellow cattle. Bioinformatic analyses of LC-MS/MS data included GO enrichment, KEGG pathway enrichment, and protein-protein interaction (PPI) analysis. Results: The results revealed 23 specific proteins in the capacitated group and 345 in the non-capacitated group. Compared with non-capacitated sperm, capacitated sperm exhibited 89 upregulated proteins and 509 downregulated proteins. Western blotting was used to confirm our proteomics data. The expression level of PSMD1 in the capacitated sperm group was significantly lower than that in the non-capacitated sperm group, and the expression level of HSPA5 was significantly higher than in the non-capacitated sperm group. Conclusions: Our results revealed that many proteins were differentially expressed between capacitated and non-capacitated sperm, particularly those involved in the proteasome signaling and protein transport signaling pathways. This work enhances our understanding of molecular processes involved in sperm viability in Yanbian yellow cattle, and provides a framework for future studies.

scholarly journals SUMO conjugation susceptibility of Akt/protein kinase B affects the expression of the pluripotency transcription factor Nanog in embryonic stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254447
Author(s):  
Marcos Francia ◽  
Martin Stortz ◽  
Camila Vazquez Echegaray ◽  
Camila Oses ◽  
Paula Verneri ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Es Cells ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Sumo Conjugation ◽  
Heterologous System ◽  
Canonical Pathways ◽  
The Impact

Akt/PKB is a kinase involved in the regulation of a wide variety of cell processes. Its activity is modulated by diverse post-translational modifications (PTMs). Particularly, conjugation of the small ubiquitin-related modifier (SUMO) to this kinase impacts on multiple cellular functions, such as proliferation and splicing. In embryonic stem (ES) cells, this kinase is key for pluripotency maintenance. Among other functions, Akt is known to promote the expression of Nanog, a central pluripotency transcription factor (TF). However, the relevance of this specific PTM of Akt has not been previously analyzed in this context. In this work, we study the effect of Akt1 variants with differential SUMOylation susceptibility on the expression of Nanog. Our results demonstrate that both, the Akt1 capability of being modified by SUMO conjugation and a functional SUMO conjugase activity are required to induce Nanog gene expression. Likewise, we found that the common oncogenic E17K Akt1 mutant affected Nanog expression in ES cells also in a SUMOylatability dependent manner. Interestingly, this outcome takes places in ES cells but not in a non-pluripotent heterologous system, suggesting the presence of a crucial factor for this induction in ES cells. Remarkably, the two major candidate factors to mediate this induction, GSK3-β and Tbx3, are non-essential players of this effect, suggesting a complex mechanism probably involving non-canonical pathways. Furthermore, we found that Akt1 subcellular distribution does not depend on its SUMOylatability, indicating that Akt localization has no influence on the effect on Nanog, and that besides the membrane localization of E17K Akt mutant, SUMOylation is also required for its hyperactivity. Our results highlight the impact of SUMO conjugation in the function of a kinase relevant for a plethora of cellular processes, including the control of a key pluripotency TF.

scholarly journals The SUMO E3 Ligase Activity of Pc2 Is Coordinated through a SUMO Interaction Motif

2010 ◽  
Vol 30 (9) ◽  
pp. 2193-2205 ◽  
Author(s):  
Shen-hsi Yang ◽  
Andrew D. Sharrocks
Keyword(s):  
Protein Modification ◽  
Binding Proteins ◽  
Noncovalent Interactions ◽  
Active Form ◽  
Embryonic Stem ◽  
E3 Ligase ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Sumo Conjugation

ABSTRACT Protein modification by SUMO conjugation has emerged to be an important regulatory event. Recently, the mechanisms through which SUMO elicits its effects on target proteins have been elucidated. One of these is the noncovalent association between SUMO and coregulatory proteins via SUMO interaction motifs (SIMs). We therefore searched for additional binding proteins to elucidate how SUMO acts as a signal to potentiate novel noncovalent interactions with SUMO-binding proteins. We identified an E3 ligase, Pc2, as a SUMO-binding protein with two functionally distinct SIMs. Here, we focus on the role of SIM2 and demonstrate that it is crucial for many of the documented Pc2 functions, which converge on determining its E3 ligase activity. One role of SUMO binding in this context is the subnuclear partitioning of the active form of Ubc9 (SUMO∼Ubc9) by Pc2. The significance of the SIM2-dependent functions of Pc2 is demonstrated in the control of the precise expression of lineage-specific genes during embryonic stem cell differentiation.

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