ECB-ART-46476
Front Physiol
January 1, 2018;
9
836.
Comparative Phospho- and Acetyl Proteomics Analysis of Posttranslational Modifications Regulating Intestine Regeneration in Sea Cucumbers.
Sun L
,
Lin C
,
Li X
,
Xing L
,
Huo D
,
Sun J
,
Zhang L
,
Yang H
.
Abstract
Sea cucumbers exposed to stressful circumstances eviscerate most internal organs, and then regenerate them rapidly under favorable environments. Reversible protein phosphorylation and acetylation are major modifications regulating protein function. Herein, for the first time, we perform quantitative phospho- and acetyl proteomics analyses of intestine regeneration in a sea cucumber species Apostichopus japonicus. We identified 1,862 phosphorylation sites in 1,169 proteins, and 712 acetylation sites in 470 proteins. Of the 147 and 251 proteins differentially modified by phosphorylation and acetylation, respectively, most were related to
cytoskeleton biogenesis, protein synthesis and modification, signal recognition and transduction, energy production and conversion, or substance transport and metabolism. Phosphorylation appears to play a more important role in signal recognition and transduction than acetylation, while acetylation is of greater importance in posttranslational modification, protein turnover, chaperones; energy production and conversion; amino acid and lipid transport and metabolism. These results expanded our understanding of the regulatory mechanisms of posttranslational modifications in intestine regeneration of sea cucumbers after evisceration.
PubMed ID:
30018572
PMC ID:
PMC6037860
Article link:
Front Physiol
Article Images:
[+] show captions
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Figure 1. Outline of the experiment design for phosphorylation and acetylation modification study. Control, the normal intestine in the sea cucumber. 3 dpe, the regenerative intestine at 3 days post evisceration.
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Figure 2. Enriched gene ontology (GO) analysis of differentially phosphorylated and acetylated proteins (p <0.05). (A) phosphorylation. (B) Acetylation. Red, GO terms of proteins for which the modification was upregulated. Green, GO terms of proteins for which the modification was downregulated.
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Figure 3. Protein domain enrichment analysis of differentially phosphorylated and acetylated proteins (p <0.05). (A) phosphorylation. (B) Acetylation. Red, Protein domain terms for which the modification was upregulated. Green, Protein domain terms for which the modification was downregulated.
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Figure 4. Enriched pathways analysis of differentially phosphorylated and acetylated proteins (all p <0.05). (A) phosphorylation. (B) Acetylation. Red, Pathways terms of proteins for which the modification was upregulated. Green, Pathways terms of proteins for which the modification was downregulated.
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Figure 5. Subcellular location of differentially phosphorylated and acetylated proteins. (A) phosphorylation. (B) acetylation. Up, subcellular location of proteins for which the modification was upregulated. Down, subcellular location of proteins for which the modification was downregulated.
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Figure 6. Schematic model of phosphorylation and acetylation during intestine regeneration in sea cucumbers. +, modification levels of almost all proteins were upregulated; −, modification levels of almost all proteins were downregulated; ±, modification levels of proteins were up- or downregulated. P, phosphorylation; Ac, acetylation; Big P or Ac, a large number of proteins were regulated by this reversible modification.
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Figure 7. Western blotting of pan-acetylation during intestine regeneration in sea cucumbers. Cell lysate samples contain 20 μg of total protein per lane. Proteins with a molecular weight of ~10 kb are likely histone family member.
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References [+] :
Arnold RJ,
The action of N-terminal acetyltransferases on yeast ribosomal proteins.
1999,
Pubmed
Arnold RJ,
The action of N-terminal acetyltransferases on yeast ribosomal proteins.
1999,
Pubmed
Cai J,
The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program.
2010,
Pubmed
Carrozza MJ,
The diverse functions of histone acetyltransferase complexes.
2003,
Pubmed
Chen M,
Comparative phosphoproteomic analysis of intestinal phosphorylated proteins in active versus aestivating sea cucumbers.
2016,
Pubmed
,
Echinobase
Cho Y,
Filamin A is required in injured axons for HDAC5 activity and axon regeneration.
2015,
Pubmed
Cohen S,
Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function.
2011,
Pubmed
Du H,
Transcriptome sequencing and characterization for the sea cucumber Apostichopus japonicus (Selenka, 1867).
2012,
Pubmed
,
Echinobase
Du Y,
Lysine malonylation is elevated in type 2 diabetic mouse models and enriched in metabolic associated proteins.
2015,
Pubmed
Duncan R,
Heat shock-induced translational alterations in HeLa cells. Initiation factor modifications and the inhibition of translation.
1984,
Pubmed
Eberharter A,
Histone acetylation: a switch between repressive and permissive chromatin. Second in review series on chromatin dynamics.
2002,
Pubmed
Franco C,
Understanding regeneration through proteomics.
2013,
Pubmed
,
Echinobase
Fujita M,
Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro.
2012,
Pubmed
García-Arrarás JE,
Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria glaberrima Selenka (Holothuroidea:Echinodermata).
1998,
Pubmed
,
Echinobase
García-Arrarás JE,
Visceral regeneration in holothurians.
2001,
Pubmed
,
Echinobase
García-Arrarás JE,
Echinoderms: potential model systems for studies on muscle regeneration.
2010,
Pubmed
,
Echinobase
García-Arrarás JE,
Regeneration of the enteric nervous system in the sea cucumber Holothuria glaberrima.
1999,
Pubmed
,
Echinobase
Gaub P,
The histone acetyltransferase p300 promotes intrinsic axonal regeneration.
2011,
Pubmed
Gillingham AK,
CASP, the alternatively spliced product of the gene encoding the CCAAT-displacement protein transcription factor, is a Golgi membrane protein related to giantin.
2002,
Pubmed
Goswami T,
Comparative phosphoproteomic analysis of neonatal and adult murine brain.
2012,
Pubmed
Grunstein M,
Histone acetylation in chromatin structure and transcription.
1997,
Pubmed
Hammond JW,
Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons.
2010,
Pubmed
He T,
Histone acetyltransferase p300 acetylates Pax5 and strongly enhances Pax5-mediated transcriptional activity.
2011,
Pubmed
Huttlin EL,
A tissue-specific atlas of mouse protein phosphorylation and expression.
2010,
Pubmed
Jeninga EH,
Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility.
2010,
Pubmed
Karin M,
Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus.
1995,
Pubmed
Keightley MC,
In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation.
2013,
Pubmed
Kim H,
Filamin A is required for vimentin-mediated cell adhesion and spreading.
2010,
Pubmed
Kim J,
A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.
2010,
Pubmed
Kouzarides T,
Acetylation: a regulatory modification to rival phosphorylation?
2000,
Pubmed
Kuzmanov U,
Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.
2016,
Pubmed
Lammers M,
Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization.
2010,
Pubmed
Li Y,
Comparative phosphoproteome analysis of Magnaporthe oryzae-responsive proteins in susceptible and resistant rice cultivars.
2015,
Pubmed
Mantovani F,
The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP.
2007,
Pubmed
Mashanov VS,
Transcriptomic changes during regeneration of the central nervous system in an echinoderm.
2014,
Pubmed
,
Echinobase
Mashanov VS,
Radial glial cells play a key role in echinoderm neural regeneration.
2013,
Pubmed
,
Echinobase
Mashanov VS,
Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration.
,
Pubmed
,
Echinobase
Miao T,
Extracellular matrix remodeling and matrix metalloproteinases (ajMMP-2 like and ajMMP-16 like) characterization during intestine regeneration of sea cucumber Apostichopus japonicus.
2017,
Pubmed
,
Echinobase
Murray G,
Myogenesis during holothurian intestinal regeneration.
2004,
Pubmed
,
Echinobase
Newton AC,
Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm.
2003,
Pubmed
Ortiz-Pineda PA,
Gene expression profiling of intestinal regeneration in the sea cucumber.
2009,
Pubmed
,
Echinobase
Pang A,
Protein acetylation and spermatogenesis.
2013,
Pubmed
Revuelta-Cervantes J,
Protein Tyrosine Phosphatase 1B (PTP1B) deficiency accelerates hepatic regeneration in mice.
2011,
Pubmed
Rojas-Cartagena C,
Distinct profiles of expressed sequence tags during intestinal regeneration in the sea cucumber Holothuria glaberrima.
2007,
Pubmed
,
Echinobase
Silva TA,
AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility.
2016,
Pubmed
Sirajuddin M,
Regulation of microtubule motors by tubulin isotypes and post-translational modifications.
2014,
Pubmed
Soppa J,
Protein acetylation in archaea, bacteria, and eukaryotes.
2010,
Pubmed
Suárez-Castillo EC,
Ependymin, a gene involved in regeneration and neuroplasticity in vertebrates, is overexpressed during regeneration in the echinoderm Holothuria glaberrima.
2004,
Pubmed
,
Echinobase
Sun L,
RNA-Seq reveals dynamic changes of gene expression in key stages of intestine regeneration in the sea cucumber Apostichopus japonicus. [corrected].
2013,
Pubmed
,
Echinobase
Sun L,
iTRAQ reveals proteomic changes during intestine regeneration in the sea cucumber Apostichopus japonicus.
2017,
Pubmed
,
Echinobase
Sun L,
Understanding regulation of microRNAs on intestine regeneration in the sea cucumber Apostichopus japonicus using high-throughput sequencing.
2017,
Pubmed
,
Echinobase
Sun L,
Large scale gene expression profiling during intestine and body wall regeneration in the sea cucumber Apostichopus japonicus.
2011,
Pubmed
,
Echinobase
Sun L,
Metabolic responses to intestine regeneration in sea cucumbers Apostichopus japonicus.
2017,
Pubmed
,
Echinobase
Sun LN,
Cloning and expression analysis of Wnt6 and Hox6 during intestinal regeneration in the sea cucumber Apostichopus japonicus.
2013,
Pubmed
,
Echinobase
Tskhovrebova L,
Titin: properties and family relationships.
2003,
Pubmed
Vassilopoulos A,
SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient- and exercise-induced stress.
2014,
Pubmed
Vetting MW,
Crystal structure of RimI from Salmonella typhimurium LT2, the GNAT responsible for N(alpha)-acetylation of ribosomal protein S18.
2008,
Pubmed
Vickery MC,
Regeneration in echinoderm larvae.
2001,
Pubmed
,
Echinobase
Yoon WJ,
Prolyl isomerase Pin1-mediated conformational change and subnuclear focal accumulation of Runx2 are crucial for fibroblast growth factor 2 (FGF2)-induced osteoblast differentiation.
2014,
Pubmed
Zhang X,
The sea cucumber genome provides insights into morphological evolution and visceral regeneration.
2017,
Pubmed
,
Echinobase
van Gorp AG,
AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B.
2009,
Pubmed
van Noort V,
Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium.
2012,
Pubmed