Post-translational modifications in proteins: resources, tools and prediction methods

Database, Journal Year: 2021, Volume and Issue: 2021

Published: Jan. 1, 2021

Posttranslational modifications (PTMs) refer to amino acid side chain modification in some proteins after their biosynthesis. There are more than 400 different types of PTMs affecting many aspects protein functions. Such happen as crucial molecular regulatory mechanisms regulate diverse cellular processes. These processes have a significant impact on the structure and function proteins. Disruption can lead dysfunction vital biological hence various diseases. High-throughput experimental methods for discovery very laborious time-consuming. Therefore, there is an urgent need computational powerful tools predict PTMs. vast amounts data, which publicly accessible through online databases. In this survey, we comprehensively reviewed major databases related tools. The current challenges were detail well.

Language: Английский

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Acetylation in the regulation of autophagy

Autophagy, Journal Year: 2022, Volume and Issue: 19(2), P. 379 - 387

Published: April 18, 2022

ABSTRACTPost-translational modifications, such as phosphorylation, ubiquitination and acetylation, play crucial roles in the regulation of autophagy. Acetylation has emerged an important regulatory mechanism for regulates autophagy initiation autophagosome formation by targeting core components ULK1 complex, BECN1-PIK3C3 LC3 lipidation system. Recent studies have shown that acetylation occurs on key proteins participating autophagic cargo assembly autophagosome-lysosome fusion, SQSTM1/p62 STX17. In addition, controls at transcriptional level histones transcription factor TFEB. Here, we review current knowledge their regulations functions pathway with focus recent findings.Abbreviations : ACAT1: acetyl-CoA acetyltransferase 1; ACSS2: acyl-CoA synthetase short chain family member 2; AMPK: AMP-activated protein kinase; ATG: autophagy-related; CALCOCO2/NDP52: calcium binding coiled-coil domain CCAR2/DBC1: cell cycle apoptosis regulator BECN1: beclin CMA: chaperone-mediated autophagy; CREBBP/CBP: CREB protein; EP300/p300: E1A p300; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3: glycogen synthase kinase 3; HDAC6: histone deacetylase 6; HSPA8/HSC70: heat shock A (Hsp70) 8; KAT2A/GCN5: lysine 2A; KAT2B/PCAF: 2B; KAT5/TIP60: 5; KAT8/MOF: LAMP2A: lysosomal associated membrane MAP1LC3/LC3: microtubule 1 light MTOR: mechanistic target rapamycin NBR1: NBR1 receptor; OPTN: optineurin; PD: Parkinson disease; PE: phosphatidylethanolamine; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type PKM2: pyruvate M1/2; PtdIns3P: phosphatidylinositol-3-phosphate; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible RUBCN/Rubicon: rubicon regulator; RUBCNL/Pacer: like enhancer; SIRT1: sirtuin SNAP29: synaptosome 29; SNARE: soluble N-ethylamide-sensitive attachment SQSTM1/p62: sequestosome STX17: syntaxin 17; TFEB: EB; TP53/p53: tumor p53; TP53INP2/DOR: p53 nuclear UBA: ubiquitin-associated; ULK1: unc-51 activating VAMP8: vesicle WIPI2: WD repeat domain, phosphoinositide interacting 2.KEYWORDS: Acetylationacetyltransferaseautophagydeacetylasepost-translational modification AcknowledgmentsWe are grateful to Dr. Do-Hyung Kim (University Minnesota, Minneapolis, US) his constructive comments careful editing work manuscript. We thank all members Wan's lab helpful discussions.Disclosure statementNo potential conflict interest was reported author(s).Additional informationFundingThis supported National Natural Science Foundation China (31970694, 31701213), Young Elite Scientists Sponsorship Program Association Technology (CAST) (2019QNRC001), Chao Kuang Piu High-tech Development Fund (2020QN024), Training Excellent Innovators Changsha (kq2106066).

Language: Английский

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Post-translational modifications in liquid-liquid phase separation: a comprehensive review

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: May 11, 2022

Abstract Liquid-liquid phase separation (LLPS) has received significant attention in recent biological studies. It refers to a phenomenon that biomolecule exceeds the solubility, condensates and separates itself from solution liquid like droplets formation. Our understanding of it also changed memebraneless organelles compartmentalization, muti-functional crucibles, reaction regulators. Although this been employed for variety processes, studies mainly focus on its physiological significance, comprehensive research underlying physical mechanism is limited. The characteristics side chains amino acids interaction tendency proteins function importantly regulating LLPS thus should be pay more on. In addition, importance post-translational modifications (PTMs) underestimated, despite their abundance crucial functions maintaining electrostatic balance. review, we first introduce driving forces protein secondary structures involved different cell life processes. Subsequently, summarize existing reports PTM regulation related analyze basic principles, hoping find some common relations between PTM. Finally, speculate several unreported PTMs may have impact basing findings.

Language: Английский

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Lactylation: a Passing Fad or the Future of Posttranslational Modification

Inflammation, Journal Year: 2022, Volume and Issue: 45(4), P. 1419 - 1429

Published: Feb. 27, 2022

Lactate is a glycolytic product and significant energy source. Moreover, it regulates gene transcription via lactylation of histones non-histone proteins, i.e., novel posttranslational modification. This review summarizes recent advances related to in lactate metabolism diseases. Notably, plays vital role cancer, inflammation, regeneration; however, the specific mechanism remains unclear. Histone oncogenic processes by targeting inflammation macrophage activation. Eventually, we identified research gaps recommended several primary directions for further studies.

Language: Английский

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Vorinostat (SAHA) and Breast Cancer: An Overview

Cancers, Journal Year: 2021, Volume and Issue: 13(18), P. 4700 - 4700

Published: Sept. 19, 2021

Vorinostat (SAHA), an inhibitor of class I and II histone deacetylases, is the first deacetylase (HDI) approved for treatment cutaneous T-cell lymphoma in 2006. HDIs are promising anticancer agents that inhibit proliferation many types cancer cells including breast carcinoma (BC). BC a heterogeneous disease with variable biological behavior, morphological features, response to therapy. Although significant progress has been made, high toxicity normal cells, serious side effects, occurrence multi-drug resistance limit effective therapy patients. Therefore, new active which improve effectiveness currently used regimens highly needed. This manuscript analyzes preclinical clinical trials data SAHA, applied individually or combination other agents, considering different histological subtypes BC.

Language: Английский

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STALLION: a stacking-based ensemble learning framework for prokaryotic lysine acetylation site prediction

Briefings in Bioinformatics, Journal Year: 2021, Volume and Issue: 23(1)

Published: Sept. 8, 2021

Protein post-translational modification (PTM) is an important regulatory mechanism that plays a key role in both normal and disease states. Acetylation on lysine residues one of the most potent PTMs owing to its critical cellular metabolism processes. Identifying protein acetylation (Kace) sites challenging task bioinformatics. To date, several machine learning-based methods for silico identification Kace have been developed. Of those, few are prokaryotic species-specific. Despite their attractive advantages performances, these certain limitations. Therefore, this study proposes novel predictor STALLION (STacking-based Predictor ProkAryotic Lysine AcetyLatION), containing six species-specific models identify accurately. extract crucial patterns around sites, we employed 11 different encodings representing three characteristics. Subsequently, systematic rigorous feature selection approach was optimal set independently five tree-based ensemble algorithms built respective baseline model each species. Finally, predicted values from were utilized trained with appropriate classifier using stacking strategy develop STALLION. Comparative benchmarking experiments showed significantly outperformed existing independent tests. expedite direct accessibility models, user-friendly online implemented, which available at: http://thegleelab.org/STALLION.

Language: Английский

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Proteomics of post-translational modifications in colorectal cancer: Discovery of new biomarkers

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1877(4), P. 188735 - 188735

Published: May 13, 2022

Language: Английский

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Liquid-liquid phase separation of protein tau: An emerging process in Alzheimer's disease pathogenesis

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 178, P. 106011 - 106011

Published: Jan. 23, 2023

Metabolic reactions within cells occur in various isolated compartments with or without borders, the latter being known as membrane-less organelles (MLOs). The MLOs show liquid-like properties and are formed by a process liquid-liquid phase separation (LLPS). contribute to different molecules interactions such protein-protein, protein-RNA, RNA-RNA driven factors, multivalency of intrinsic disorders. involved several cell signaling pathways transcription, immune response, cellular organization. However, disruption these processes has been found pathologies. Recently, it demonstrated that protein aggregates, characteristic some neurodegenerative diseases, undergo similar separation. Tau is major neurofibrillary tangles component Alzheimer's disease (AD). This can form MLO tau droplet vitro vivo, this be facilitated including crowding agents, RNA, phosphorylation. shown mature into insoluble aggregates suggesting may precede induce neurodegeneration AD. Here we review factors liquid formation cell. Additionally, highlight recent findings concerning aggregation following AD, along potential therapeutic strategies could explored against progression pathology.

Language: Английский

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Critical Role of histone deacetylase 3 in the regulation of kidney inflammation and fibrosis

Kidney International, Journal Year: 2024, Volume and Issue: 105(4), P. 775 - 790

Published: Jan. 28, 2024

Language: Английский

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Identification of molecular determinants of gene-specific bursting patterns by high-throughput imaging screens

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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