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torsdag 18 oktober 2018

Artikkeli ajateltavaksi

Dietäärisen SFA.n vaikutus  NLRP3 inflammasomiin ja Il-1B statukseen.
https://www.cell.com/cell-reports/fulltext/S2211-1247(16)30174-7

onsdag 8 augusti 2018

Plasmalogeenit sammaleläinlajissa . Plasmalogeenikardiomyosyytissä.

Sammaleläinlajista Pectinella magnifica löytyy  hyvin runsans  PUDFA- happojohdannasi sisältö plasmalogeenimuotoisina.


2.
Řezanka T, Vítová M, Lukavský J, Sigler K.
Lipids. 2018 Apr;53(4):413-427. doi: 10.1002/lipd.12039. Epub 2018 Apr 30.
PMID:
29709080
Similar articles

 5

fredag 3 augusti 2018

Histoni- K- krotonylaatio - vasta keksitty modifikaatio . SIRT 3 on dekrotonylaasi.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920150/

Dis Model Mech. 2016 Jun 1; 9(6): 633–645.
PMCID: PMC4920150
PMID: 27125278

Histone lysine crotonylation during acute kidney injury in mice

ABSTRACT
Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. 

Post-translational histone modifications modulate gene expression and kidney injury. 
Histone crotonylation is a recently described post-translational modification. 

We hypothesized that histone crotonylation might modulate kidney injury.

Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin.

 Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue
Kidney tissue histone crotonylation increased during AKI.
This was reproduced by exposure to the protein TWEAK in cultured tubular cells.

 Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue.

 To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys.

 Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression.

 For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state.

KEY WORDS: Acute kidney injury, Epigenetics, Histone, Inflammation, Tubular cell

K-krotonylaatio

http://www.mcponline.org/content/early/2018/07/18/mcp.RA118.000640

Global involvement of lysine crotonylation in protein modification and transcription regulation in rice

  1. 1Yangzhou University, China
  2. 2Nanjing Agricultural University, China
  3. 3Jingjie PTM Biolabs (Hangzhou) Co. Ltd
  4. 4Fujian Agriculture and Forestry University, China
  1. * Corresponding Author:
    Zhiyun Gong, Yangzhou University, China. E-mail: zygong{at}yzu.edu.cn
Abstract
Lysine crotonylation (Kcr) is a newly discovered post-translational modification (PTM) existing in mammals.
A global crotonylome analysis was undertaken in rice (Oryza sativa L. japonica) using high accuracy nano-LC-MS/MS in combination with crotonylated peptide enrichment. A total of 1,265 lysine crotonylation sites were identified on 690 proteins in rice seedlings. Subcellular localization analysis revealed that 51% of the crotonylated proteins identified were localized in chloroplasts. The photosynthesis-associated proteins were also mostly enriched in total crotonylated proteins.
 In addition, a genomic localization analysis of histone Kcr by ChIP-seq was performed to assess the relevance between histone Kcr and the genome. Of the 10,923 identified peak regions, the majority (86.7%) of the enriched peaks were located in gene body, especially exons. Furthermore, the degree of histone Kcr modification was positively correlated with gene expression in genic regions. Compared with other published histone modification data, the Kcr was co-located with the active histone modifications. Interestingly, histone Kcr facilitated expression of genes with existing active histone modifications. In addition, 77% of histone Kcr modifications overlapped with DNase hypersensitive sites (DHSs) in intergenic regions of the rice genome, and might mark other cis-regulatory DNA elements which are different from IPA1, a transcription activator in rice seedlings.
 Overall, our results provide a comprehensive understanding of the biological functions of the crotonylome and new active histone modification in transcriptional regulation in plants.

Proteiinien K-asylaatiosta yleensä

2018 

https://www.ncbi.nlm.nih.gov/pubmed/29887264
Xu JY, Xu Y, Xu Z, Zhai LH, Ye Y, Zhao Y, Chu X, Tan M, Ye BC.
Cell Chem Biol. 2018 May 21. pii: S2451-9456(18)30152-1. doi: 10.1016/j.chembiol.2018.05.005. [Epub ahead of print] PMID: 29887264
2.
Revealing the protein propionylation activity of the histone acetyltransferase MOF (males absent on the first). Han Z, Wu H, Kim S, Yang X, Li Q, Huang H, Cai H, Bartlett MG, Dong A, Zeng H, Brown PJ, Yang XJ, Arrowsmith CH, Zhao Y, Zheng YG.
J Biol Chem. 2018 Mar 2;293(9):3410-3420. doi: 10.1074/jbc.RA117.000529. Epub 2018 Jan 10. PMID: 29321206
3.
Liu X, Wei W, Liu Y, Yang X, Wu J, Zhang Y, Zhang Q, Shi T, Du JX, Zhao Y, Lei M, Zhou JQ, Li J, Wong J. Cell Discov. 2017 May 23;3:17016. doi: 10.1038/celldisc.2017.16. eCollection 2017. PMID:28580166
".. Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation."
4.
Nie L, Shuai L, Zhu M, Liu P, Xie ZF, Jiang S, Jiang HW, Li J, Zhao Y, Li JY, Tan M.
Mol Cell Proteomics. 2017 Jul;16(7):1324-1334. doi: 10.1074/mcp.M117.067553. Epub 2017 Apr 27.PMID:28450421
".. Type 2 diabetes (T2D) is a major chronic healthcare concern worldwide. Emerging evidence suggests that a histone-modification-mediated epigenetic mechanism underlies T2D."
5.
Li QQ, Hao JJ, Zhang Z, Krane LS, Hammerich KH, Sanford T, Trepel JB, Neckers L, Agarwal PK.
Sci Rep. 2017 Mar 15;7(1):201. doi: 10.1038/s41598-017-00143-6. PMID: 28298630
".. Furthermore, quantitative proteome studies identified 14 types of PTMs with 93 marks on the core histones, including 34 novel histone marks of butyrylation, citrullination, 2-hydroxyisobutyrylation, methylation, O-GlcNAcylation, propionylation, and succinylation in AUY922- and ganetespib-treated 5637 cells".
6.
Pelletier N, Grégoire S, Yang XJ.
Curr Protoc Protein Sci. 2017 Feb 2;87:14.11.1-14.11.18. doi: 10.1002/cpps.26.  PMID:28150880
".. Lysine acetylation refers to addition of an acetyl moiety to the epsilon-amino group of a lysine residue and is important for regulating protein functions in various organisms from bacteria to humans. This is a reversible and precisely controlled covalent modification that either serves as an on/off switch or participates in a codified manner with other post-translational modifications to regulate different cellular and developmental processes in normal and pathological states. This unit describes methods for in vitro and in vivo determination of lysine acetylation. Such methods can be easily extended for analysis of other acylations (such as propionylation, butyrylation, crotonylation, and succinylation) that are also present in histones and many other proteins."
7.
Sabari BR, Zhang D, Allis CD, Zhao Y.
Nat Rev Mol Cell Biol. 2017 Feb;18(2):90-101. doi: 10.1038/nrm.2016.140. Epub 2016 Dec 7. Review. PMID:  27924077
" Eight types of short-chain Lys acylations have recently been identified on histones: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. Emerging evidence suggests that these histone modifications affect gene expression and are structurally and functionally different from the widely studied histone Lys acetylation. In this Review, we discuss the regulation of non-acetyl histone acylation by enzymatic and metabolic mechanisms, the acylation 'reader' proteins that mediate the effects of different acylations and their physiological functions, which include signal-dependent gene activation, spermatogenesis, tissue injury and metabolic stress. We propose a model to explain our present understanding of how differential histone acylation is regulated by the metabolism of the different acyl-CoA forms, which in turn modulates the regulation of gene expression".
8.
Sun M, Xu J, Wu Z, Zhai L, Liu C, Cheng Z, Xu G, Tao S, Ye BC, Zhao Y, Tan M.
J Proteome Res. 2016 Dec 2;15(12):4696-4708. Epub 2016 Nov 10.PMID:27804304
", we identified 1467 lysine propionylation sites in 603 proteins in E. coli. Quantitative propionylome analysis further revealed that global lysine propionylation level was drastically increased in response to propionate treatment,.."
9.
Xiong X, Panchenko T, Yang S, Zhao S, Yan P, Zhang W, Xie W, Li Y, Zhao Y, Allis CD, Li H.
Nat Chem Biol. 2016 Dec;12(12):1111-1118. doi: 10.1038/nchembio.2218. Epub 2016 Oct 24. PMID: 27775714
".. Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr.
10.
Li Y, Sabari BR, Panchenko T, Wen H, Zhao D, Guan H, Wan L, Huang H, Tang Z, Zhao Y, Roeder RG, Shi X, Allis CD, Li H.Mol Cell. 2016 Apr 21;62(2):181-193. doi: 10.1016/j.molcel.2016.03.028.PMID: 27105114Free PMC Article
" Recognition of histone covalent modifications by chromatin-binding protein modules ("readers") constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g., crotonylation, butyrylation, propionylation) have been recently identified, but readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyllysine over acetyllysine."
11.
Wu Z, Cheng Z, Sun M, Wan X, Liu P, He T, Tan M, Zhao Y.
Mol Cell Proteomics. 2015 Feb;14(2):329-39. doi: 10.1074/mcp.M114.044255. Epub 2014 Dec 11.PMID:25505155
12.
Tooley JG, Schaner Tooley CE.
Protein Sci. 2014 Dec;23(12):1641-9. doi: 10.1002/pro.2547. Epub 2014 Sep 26. Review.PMID:25209108
".. Historically considered static regulators of protein stability, additional functional roles for N-terminal PTMs are now beginning to be elucidated. New findings show that N-terminal methylation, along with N-terminal acetylation, is an important regulatory modification with significant roles in development and disease progression.There are also emerging studies on the enzymology and functional roles of N-terminal ubiquitylation and N-terminal propionylation.
13.
Lee S.Toxicol Res. 2013 Jun;29(2):81-6. doi: 10.5487/TR.2013.29.2.081. Review. PMID:24278632
".. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer."
14.
Singh B, Boopathy S, Somasundaram K, Umapathy S.
J Biophotonics. 2012 Mar;5(3):230-9. doi: 10.1002/jbio.201100061. Epub 2012 Jan 19. PMID:22259119
"Histone deacetylase inhibitors (HDIs) have attracted considerable attention as potential drug molecules in tumour biology. In order to optimise chemotherapy, it is important to understand the mechanisms of regulation of histone deacetylase (HDAC) enzymes and modifications brought by various HDIs."

Proteiinin K-propionylaatio, MYST perhe

https://www.ncbi.nlm.nih.gov/pubmed/29321206
Tapahtuuko propionylaatiota  ihmissolussakin? Bakteereissahan ilmiö on yleinen.

LÄHDE:  J Biol Chem. 2018 Mar 2;293(9):3410-3420. doi: 10.1074/jbc.RA117.000529. Epub 2018 Jan 10. Revealing the protein propionylation activity of the histone acetyltransferase MOF (males absent on the first). Han Z1, Wu H2, Kim S3, Yang X1, Li Q1, Huang H3, Cai H1, Bartlett MG1, Dong A2, Zeng H2, Brown PJ2, Yang XJ4, Arrowsmith CH2,5, Zhao Y3, Zheng YG6. Abstract (suomenosta) 
Lysiinitähteiden (K) asyloituminen lyhyillä rasvahapoilla (SCFA) on havaittu olevan eräs  palautuvista posttranslationaalisista modifikaatioista imettäväissoluissa.  Asylaatioitten  moninaisuus  laajentaa käsityksiä proteosomaalisesta maisemasta ja kompleksisuudesta.  Näiden ilmiöiden molekyylitason käsittämisessä on olennaisen tärkeää tunnistaa  lysiinin (K) asylaatiota säätelevät entsyymit ja effektoriproteiinit. Tässä artikelissaan tutkijat  raportoivat  lysiiniasyylitransferaasien (KAT)  eräästä histoniasetylaasiperheestä MYST,  jolla on vahvaa propionyylitransferaasiaktiivisuutta  sekä in vitro että in cellulo. . 
Erityisesti  MYST perheenjäsenilla  MOF (KAT8) , MOZ ja HBO1 on propionyylitransferaasiaktiivisuus yhtä vahvaa kuin niiden  asetyylitransferaasiaktiivisuus. Kun MOF  on yli-ilmentymässä alkion munuaissoluissa 293T  se indusoi monissa histoneissa ja ei-histoniproteiineissa merkitsevästi lisääntynyttä  propionylaatiota, mikä  ulottuu paljon laajemmalle funktioalueelle kuin MOF:in  kanoninen histonin H4 lysiinin K16 asetylaatio. 
Tutkijat selvittivät myös MOF entsyymiin kiderakenteen kun se on sitoutuneena propionyyliCoA:n kanssa, mistä  tarjoutuu suora rakenteellinen perusta  MYST perheen  KAT entsyymien propionyylitransferaasiaktiivisuudelle.  Nämä tiedot  yhdessä määrittävät  MYST KAT:entsyymien uuden funktion lysiini-propionyylitransferaaseina  ja  viittaavat paljon laajempaan fysiologiseen vaikutukseen, mitä tämän ryhmän entsyymeillä on tiedetty olevan.

  • Short-chain acylation of lysine residues has recently emerged as a group of reversible posttranslational modifications in mammalian cells. The diversity of acylation further broadens the landscape and complexity of the proteome. Identification of regulatory enzymes and effector proteins for lysine acylation is critical to understand functions of these novel modifications at the molecular level. Here, we report that the MYST family of lysine acetyltransferases (KATs) possesses strong propionyltransferase activity both in vitro and in cellulo Particularly, the propionyltransferase activity of MOF, MOZ, and HBO1 is as strong as their acetyltransferase activity. Overexpression of MOF in human embryonic kidney 293T cells induced significantly increased propionylation in multiple histone and non-histone proteins, which shows that the function of MOF goes far beyond its canonical histone H4 lysine 16 acetylation. We also resolved the X-ray co-crystal structure of MOF bound with propionyl-coenzyme A, which provides a direct structural basis for the propionyltransferase activity of the MYST KATs. Our data together define a novel function for the MYST KATs as lysine propionyltransferases and suggest much broader physiological impacts for this family of enzymes.
KEYWORDS:
Males absent on the first (MOF); MOF entsyymi, MYST perheenjäsen , K-asetyylitransferaasi
 acetyltransferase; asetyylitransferaasi
 crystal structure; kiderakenne
 lysine propionylation; lysiinipropionylaatio , K-propionylaatio
 post-translational modification (PTM); translaationjälkeinen modifikaatio
 protein acylation;  proteiinin asylaatio, happotähteen liitto proteiiniin
proteomics

PMCID:
PMC5836141
[Available on 2019-03-02]
DOI:
10.1074/jbc.RA117.000529
Lisätieto KAT8- geeni (16p11.2)  antaa  katsausta  jo tunetusta asetyylitransferaasivaikutuksesta, mutta tässä ei ole vielä  erityisiä kliinisiä artikkeleita  propionylaatioista. 

https://www.ncbi.nlm.nih.gov/gene/84148
  • Also known as MOF; hMOF; MYST1; ZC2HC8
  •  
  • Preferred Names
    histone acetyltransferase KAT8
    Names
    K(lysine) acetyltransferase 8
    MOZ, YBF2/SAS3, SAS2 and TIP60 protein 1
    MYST histone acetyltransferase 1
    MYST-1
    histone acetyltransferase MYST1
    ortholog of Drosophila males absent on the first (MOF)
    probable histone acetyltransferase MYST1
  • Summary This gene encodes a member of the MYST histone acetylase protein family. The encoded protein has a characteristic MYST domain containing an acetyl-CoA-binding site, a chromodomain typical of proteins which bind histones, and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]
  • Expression Ubiquitous expression in ovary (RPKM 17.1), testis (RPKM 11.9) and 25 other tissues See more Orthologs mouse all 
  • Related Articles in Pub Med
  • Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation. McCullough CE, et al. J Biol Chem, 2016 Aug 26. PMID 27382063, Free PMC Article
  •  
  • KAT8 Regulates Androgen Signaling in Prostate Cancer Cells. Kim JY, et al. Mol Endocrinol, 2016 Aug. PMID 27268279, Free PMC ArticleAndrogen receptor (AR) plays pivotal roles in prostate cancer. Upon androgen stimulation, AR recruits the Protein kinase N1 (PKN1), which phosphorylates histone H3 at threonine 11, with subsequent recruitment of tryptophan, aspartic acid (WD) repeat-containing protein 5 (WDR5) and the su(var)3-9, enhancer of zeste, trithorax/mixed-lineage leukemia (SET1/MLL) histone methyltransferase complex to promote AR target gene activation and prostate cancer cell grow However, the underlying mechanisms of target gene activation and cell growth subsequent to WDR5 recruitment are not well understood. Here, we demonstrate an epigenetic cross talk between histone modifications and AR target gene regulation. We discovered that K(lysine) acetyltransferase 8 (KAT8), a member of the MOZ, YBF2/SAS2, and TIP 60 protein 1 (MYST) family of histone acetyltransferases that catalyzes histone H4 lysine 16 acetylation, colocalized with WDR5 at AR target genes, resulting in hormone-dependent gene activation in prostate cancer cells. PKN1 or WDR5 knockdown severely inhibited KAT8 association with AR target genes and histone H4 lysine 16 acetylation upon androgen treatment. Knockdown of KAT8 significantly decreased AR target gene expression and prostate cancer cell proliferation. Collectively, these data describe a trans-histone modification pathway involving PKN1/histone H3 threonine 11 phosphorylation followed by WDR5/MLL histone methyltransferase and KAT8/histone acetyltransferase recruitment to effect androgen-dependent gene activation and prostate cancer cell proliferation. 
  • A multifaceted role for MOF histone modifying factor in genome maintenance. Mujoo K, et al. Mech Ageing Dev, 2017 Jan. PMID 27038808, Free PMC Article For example, recent results indicate MOF is an upstream regulator of the ATM (ataxia-telangiectasia mutated) protein, the loss of which is responsible for ataxia telangiectasia (AT). ATM is a key regulatory kinase that interacts with and phosphorylates multiple substrates that influence critical, cell-cycle control and DNA damage repair pathways in addition to other pathways. Thus, directly or indirectly, MOF may be involved in a wide range of cellular functions. This review will focus on the contribution of MOF to cellular DNA repair and new results that are beginning to examine the in vivo physiological role of MOF. 
  • The Histone Acetyltransferase MOF Promotes Induces Generation of Pluripotent Stem Cells. Mu X, et al. Cell Reprogram, 2015 Aug. PMID 2609136In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming. 
  • Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma. Zhu L, et al. Int J Oncol, 2015. PMID 25873202 
  • See all (73) citations in PubMed See citations in PubMed for homologs of this gene provided by HomoloGene
  •  See all GeneRIFs (43)
  • 3.8. 2018 
  • onsdag 1 augusti 2018

    LIPA geeni (10q23.31),LAL, Lipase A, lysosomaali happotyyppinen, Kolesteroliesterihydrolaasi (CESD)

    https://www.ncbi.nlm.nih.gov/gene/3988
    Also known as
    LAL; CESD
    Summary
    This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]
    Expression
    Broad expression in spleen (RPKM 177.6), small intestine (RPKM 113.4) and 21 other tissues See more

    Related articles in PubMed