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 8MOZ, YBF2/SAS3, SAS2 and TIP60 protein 1MYST histone acetyltransferase 1MYST-1histone acetyltransferase MYST1ortholog 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
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We discovered that K(lysine) acetyltransferase 8 (KAT8), a member of the
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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
