scholarly journals Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes

2006 ◽  
Vol 173 (4) ◽  
pp. 463-468 ◽  
Author(s):  
Susan M. Millard ◽  
Stephen A. Wood
Keyword(s):  
Protein Trafficking ◽  
Protein Localization ◽  
Ubiquitin Ligases ◽  
Current Evidence ◽  
Clear Understanding ◽  
Dependent Protein ◽  
Regulate Protein

Ubiquitylation is a key regulator of protein trafficking, and much about the functions of ubiquitin ligases, which add ubiquitin to substrates in this regulation, has recently come to light. However, a clear understanding of ubiquitin-dependent protein localization cannot be achieved without knowledge of the role of deubiquitylating enzymes (DUBs). DUBs, by definition, function downstream in ubiquitin pathways and, as such, have the potential to be the final editors of protein ubiquitylation status, thus determining substrate fate. This paper assimilates the current evidence concerning the substrates and activities of DUBs that regulate protein trafficking.

scholarly journals The Role of Posttranslational Modifications in DNA Repair

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Protein Localization ◽  
Complex Structure ◽  
Protein Protein Interactions ◽  
Regulate Protein

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

Towards a mechanistic understanding of competence: a missing link in diversity–disease research

Parasitology ◽  
2020 ◽  
Vol 147 (11) ◽  
pp. 1159-1170 ◽  
Author(s):  
Tara E. Stewart Merrill ◽  
Pieter T. J. Johnson
Keyword(s):  
Infectious Disease ◽  
Community Ecology ◽  
Dilution Effect ◽  
Biodiversity Loss ◽  
Current Evidence ◽  
Clear Understanding ◽  
Future Directions ◽  
Disease Research ◽  
Mechanistic Understanding

AbstractBiodiversity loss may increase the risk of infectious disease in a phenomenon known as the dilution effect. Circumstances that increase the likelihood of disease dilution are: (i) when hosts vary in their competence, and (ii) when communities disassemble predictably, such that the least competent hosts are the most likely to go extinct. Despite the central role of competence in diversity–disease theory, we lack a clear understanding of the factors underlying competence, as well as the drivers and extent of its variation. Our perspective piece encourages a mechanistic understanding of competence and a deeper consideration of its role in diversity–disease relationships. We outline current evidence, emerging questions and future directions regarding the basis of competence, its definition and measurement, the roots of its variation and its role in the community ecology of infectious disease.

scholarly journals LINE-1 and the cell cycle: protein localization and functional dynamics

2017 ◽  
Author(s):  
Paolo Mita ◽  
Aleksandra Wudzinska ◽  
Xiaoji Sun ◽  
Joshua Andrade ◽  
Shruti Nayak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Human Genome ◽  
Cell Biology ◽  
Protein Localization ◽  
Clear Understanding ◽  
Cell Cycle Protein ◽  
Functional Dynamics ◽  
Human Genomic ◽  
The Many

AbstractLINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology to aid its proliferation. However, a clear understanding of L1’s lifecycle and the processes involved in restricting its insertion and its intragenomic spreading remains elusive. Here we identify modes of L1 proteins’ entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

scholarly journals LINE-1 protein localization and functional dynamics during the cell cycle

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Paolo Mita ◽  
Aleksandra Wudzinska ◽  
Xiaoji Sun ◽  
Joshua Andrade ◽  
Shruti Nayak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Human Genome ◽  
Cell Biology ◽  
Protein Localization ◽  
Clear Understanding ◽  
Functional Dynamics ◽  
Human Genomic ◽  
The Many ◽  
L1 Retrotransposon

LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology. However, a clear understanding of L1’s lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins’ entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells

2009 ◽  
pp. 1-8
Author(s):  
Jing-Lei Qu ◽  
Xiu-Juan Qu ◽  
Ming-Fang Zhao ◽  
Yue-E Teng ◽  
Ye Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Ubiquitin Ligases ◽  
Jurkat T Cells ◽  
Induced Apoptosis

Using serum biomarkers for identifying unstable carotid plaque: update of current evidence

2020 ◽  
Vol 26 ◽  
Author(s):  
Areti Sofogianni ◽  
Konstantinos Tziomalos ◽  
Triantafyllia Koletsa ◽  
Apostolos G. Pitoulias ◽  
Lemonia Skoura ◽  
...  
Keyword(s):  
High Risk ◽  
Great Proportion ◽  
Current Literature ◽  
Early Identification ◽  
Carotid Plaque ◽  
Potential Role ◽  
Carotid Atherosclerosis ◽  
Serum Biomarkers ◽  
Current Evidence

: Carotid atherosclerosis is responsible for a great proportion of ischemic strokes. Early identification of unstable or vulnerable carotid plaques and therefore of patients at high risk for stroke is of significant medical and socioeconomical value. We reviewed the current literature and discuss the potential role of the most important serum biomarkers in identifying patients with carotid atherosclerosis who are at high risk for atheroembolic stroke.

Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations

2020 ◽  
Vol 18 (2) ◽  
pp. 135-150
Author(s):  
Harsha S. Nagarajarao ◽  
Chandra P. Ojha ◽  
Archana Kedar ◽  
Debabrata Mukherjee
Keyword(s):  
Patent Foramen Ovale ◽  
Cryptogenic Stroke ◽  
Narrow Channel ◽  
Paradoxical Embolism ◽  
Current Evidence ◽  
Foramen Ovale ◽  
The Right ◽  
The Relationship ◽  
Current Guidelines

: Cryptogenic stroke and its relation to the Patent Foramen Ovale (PFO) is a long-debated topic. Recent clinical trials have unequivocally established the relationship between cryptogenic strokes and paradoxical embolism across the PFO. This slit-like communication exists in everyone before birth, but most often closes shortly after birth. PFO may persist as a narrow channel of communication between the right and left atria in approximately 25-27% of adults. : In this review, we examine the clinical relevance of the PFO with analysis of the latest trials evaluating catheter-based closure of PFO’s for cryptogenic stroke. We also review the current evidence examining the use of antiplatelet medications versus anticoagulants for stroke prevention in those patients with PFO who do not qualify for closure per current guidelines.

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