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 CH^2,5, 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

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3.8. 2018