The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6

The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyltRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found tha...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2021-01, Vol.118 (1), p.1-11
Hauptverfasser: Arva, Akshaya, Kasu, Yasar Arfat T., Duncan, Jennifer, Alkhatatbeh, Mosleh A., Brower, Christopher S.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 11
container_issue 1
container_start_page 1
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 118
creator Arva, Akshaya
Kasu, Yasar Arfat T.
Duncan, Jennifer
Alkhatatbeh, Mosleh A.
Brower, Christopher S.
description The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyltRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid–liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.
doi_str_mv 10.1073/pnas.2015887118
format Article
fullrecord <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7817205</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>27006438</jstor_id><sourcerecordid>27006438</sourcerecordid><originalsourceid>FETCH-LOGICAL-c443t-1f75fc9799d22cd530088fec02d8471fd95357f2c2ef497da84313d9415acde63</originalsourceid><addsrcrecordid>eNpdkUtvEzEUhS0EoqGwZgWyxIbNtNePGdsbpCq8FYlNWVuu7UkcTezBnqmUP8DvxqOU8Fjdxf3O0Tk6CL0kcEVAsOsxmnJFgbRSCkLkI7QioEjTcQWP0QqAikZyyi_Qs1L2AKBaCU_RBWOcM8K7Ffp5u_N4E7YmOpx6fDN5gkPBIU45xBKsGYYjdqGk7Hz2Di_caPIUbBjN5BcSx9kOPg0m43FnisfFV8JMIUWc_XYeKufw3RF_nQ8p7gN-nw6mytYpTvWGuMXdc_SkN0PxLx7uJfr-8cPt-nOz-fbpy_pm09gaeGpIL9reKqGUo9S6lgFI2XsL1EkuSO9Uy1rRU0t9z5VwRtaazClOWmOd79glenfyHee7g3fW155m0GMOB5OPOpmg__3EsNPbdK-FJIJCWw3ePhjk9GP2ZdKHUKwfBhN9moumXEjgRBFV0Tf_ofs051jrLRTjVPJuSXR9omxOpWTfn8MQ0MvGetlY_9m4Kl7_3eHM_x61Aq9OwL5MKZ__VAB0nEn2C39xrpo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473428466</pqid></control><display><type>article</type><title>The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Arva, Akshaya ; Kasu, Yasar Arfat T. ; Duncan, Jennifer ; Alkhatatbeh, Mosleh A. ; Brower, Christopher S.</creator><creatorcontrib>Arva, Akshaya ; Kasu, Yasar Arfat T. ; Duncan, Jennifer ; Alkhatatbeh, Mosleh A. ; Brower, Christopher S.</creatorcontrib><description>The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyltRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid–liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2015887118</identifier><identifier>PMID: 33443146</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Aminoacyltransferases - metabolism ; Animals ; Biological Sciences ; Cell Nucleolus - metabolism ; Domains ; Fluorescence ; HEK293 Cells ; Humans ; Hydroxylase ; Immunocytochemistry ; Intrinsically Disordered Proteins - chemistry ; Intrinsically Disordered Proteins - metabolism ; Jumonji Domain-Containing Histone Demethylases - metabolism ; Ligands ; Liquid phases ; Liquid-Liquid Extraction - methods ; Mice ; Nuclear Proteins - metabolism ; Nucleoli ; Phase separation ; Phase Transition ; Protein Binding ; Protein Domains ; Proteins ; Proteolysis ; Receptors, Cell Surface - metabolism ; tRNA</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-01, Vol.118 (1), p.1-11</ispartof><rights>Copyright National Academy of Sciences Jan 5, 2021</rights><rights>2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-1f75fc9799d22cd530088fec02d8471fd95357f2c2ef497da84313d9415acde63</citedby><cites>FETCH-LOGICAL-c443t-1f75fc9799d22cd530088fec02d8471fd95357f2c2ef497da84313d9415acde63</cites><orcidid>0000-0003-4836-7437 ; 0000-0002-1627-7261 ; 0000-0002-9057-1186 ; 0000-0003-2690-3729</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27006438$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27006438$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33443146$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arva, Akshaya</creatorcontrib><creatorcontrib>Kasu, Yasar Arfat T.</creatorcontrib><creatorcontrib>Duncan, Jennifer</creatorcontrib><creatorcontrib>Alkhatatbeh, Mosleh A.</creatorcontrib><creatorcontrib>Brower, Christopher S.</creatorcontrib><title>The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyltRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid–liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.</description><subject>Aminoacyltransferases - metabolism</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cell Nucleolus - metabolism</subject><subject>Domains</subject><subject>Fluorescence</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Hydroxylase</subject><subject>Immunocytochemistry</subject><subject>Intrinsically Disordered Proteins - chemistry</subject><subject>Intrinsically Disordered Proteins - metabolism</subject><subject>Jumonji Domain-Containing Histone Demethylases - metabolism</subject><subject>Ligands</subject><subject>Liquid phases</subject><subject>Liquid-Liquid Extraction - methods</subject><subject>Mice</subject><subject>Nuclear Proteins - metabolism</subject><subject>Nucleoli</subject><subject>Phase separation</subject><subject>Phase Transition</subject><subject>Protein Binding</subject><subject>Protein Domains</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>tRNA</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtvEzEUhS0EoqGwZgWyxIbNtNePGdsbpCq8FYlNWVuu7UkcTezBnqmUP8DvxqOU8Fjdxf3O0Tk6CL0kcEVAsOsxmnJFgbRSCkLkI7QioEjTcQWP0QqAikZyyi_Qs1L2AKBaCU_RBWOcM8K7Ffp5u_N4E7YmOpx6fDN5gkPBIU45xBKsGYYjdqGk7Hz2Di_caPIUbBjN5BcSx9kOPg0m43FnisfFV8JMIUWc_XYeKufw3RF_nQ8p7gN-nw6mytYpTvWGuMXdc_SkN0PxLx7uJfr-8cPt-nOz-fbpy_pm09gaeGpIL9reKqGUo9S6lgFI2XsL1EkuSO9Uy1rRU0t9z5VwRtaazClOWmOd79glenfyHee7g3fW155m0GMOB5OPOpmg__3EsNPbdK-FJIJCWw3ePhjk9GP2ZdKHUKwfBhN9moumXEjgRBFV0Tf_ofs051jrLRTjVPJuSXR9omxOpWTfn8MQ0MvGetlY_9m4Kl7_3eHM_x61Aq9OwL5MKZ__VAB0nEn2C39xrpo</recordid><startdate>20210105</startdate><enddate>20210105</enddate><creator>Arva, Akshaya</creator><creator>Kasu, Yasar Arfat T.</creator><creator>Duncan, Jennifer</creator><creator>Alkhatatbeh, Mosleh A.</creator><creator>Brower, Christopher S.</creator><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4836-7437</orcidid><orcidid>https://orcid.org/0000-0002-1627-7261</orcidid><orcidid>https://orcid.org/0000-0002-9057-1186</orcidid><orcidid>https://orcid.org/0000-0003-2690-3729</orcidid></search><sort><creationdate>20210105</creationdate><title>The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6</title><author>Arva, Akshaya ; Kasu, Yasar Arfat T. ; Duncan, Jennifer ; Alkhatatbeh, Mosleh A. ; Brower, Christopher S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-1f75fc9799d22cd530088fec02d8471fd95357f2c2ef497da84313d9415acde63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aminoacyltransferases - metabolism</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Cell Nucleolus - metabolism</topic><topic>Domains</topic><topic>Fluorescence</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Hydroxylase</topic><topic>Immunocytochemistry</topic><topic>Intrinsically Disordered Proteins - chemistry</topic><topic>Intrinsically Disordered Proteins - metabolism</topic><topic>Jumonji Domain-Containing Histone Demethylases - metabolism</topic><topic>Ligands</topic><topic>Liquid phases</topic><topic>Liquid-Liquid Extraction - methods</topic><topic>Mice</topic><topic>Nuclear Proteins - metabolism</topic><topic>Nucleoli</topic><topic>Phase separation</topic><topic>Phase Transition</topic><topic>Protein Binding</topic><topic>Protein Domains</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>tRNA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arva, Akshaya</creatorcontrib><creatorcontrib>Kasu, Yasar Arfat T.</creatorcontrib><creatorcontrib>Duncan, Jennifer</creatorcontrib><creatorcontrib>Alkhatatbeh, Mosleh A.</creatorcontrib><creatorcontrib>Brower, Christopher S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arva, Akshaya</au><au>Kasu, Yasar Arfat T.</au><au>Duncan, Jennifer</au><au>Alkhatatbeh, Mosleh A.</au><au>Brower, Christopher S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2021-01-05</date><risdate>2021</risdate><volume>118</volume><issue>1</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The Ligand of Ate1 (Liat1) is a protein of unknown function that was originally discovered through its interaction with arginyltRNA protein transferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation. Here, we characterized the functional domains of mouse Liat1 and found that its N-terminal half comprises an intrinsically disordered region (IDR) that facilitates its liquid–liquid phase separation (LLPS) in the nucleolus. Using bimolecular fluorescence complementation and immunocytochemistry, we found that Liat1 is targeted to the nucleolus by a low-complexity poly-K region within its IDR. We also found that the lysyl-hydroxylase activity of Jumonji Domain Containing 6 (Jmjd6) modifies Liat1, in a manner that requires the Liat1 poly-K region, and inhibits its nucleolar targeting and potential functions. In sum, this study reveals that Liat1 participates in nucleolar LLPS regulated by Jmjd6.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>33443146</pmid><doi>10.1073/pnas.2015887118</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-4836-7437</orcidid><orcidid>https://orcid.org/0000-0002-1627-7261</orcidid><orcidid>https://orcid.org/0000-0002-9057-1186</orcidid><orcidid>https://orcid.org/0000-0003-2690-3729</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0027-8424
ispartof Proceedings of the National Academy of Sciences - PNAS, 2021-01, Vol.118 (1), p.1-11
issn 0027-8424
1091-6490
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7817205
source MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Aminoacyltransferases - metabolism
Animals
Biological Sciences
Cell Nucleolus - metabolism
Domains
Fluorescence
HEK293 Cells
Humans
Hydroxylase
Immunocytochemistry
Intrinsically Disordered Proteins - chemistry
Intrinsically Disordered Proteins - metabolism
Jumonji Domain-Containing Histone Demethylases - metabolism
Ligands
Liquid phases
Liquid-Liquid Extraction - methods
Mice
Nuclear Proteins - metabolism
Nucleoli
Phase separation
Phase Transition
Protein Binding
Protein Domains
Proteins
Proteolysis
Receptors, Cell Surface - metabolism
tRNA
title The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T21%3A37%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Ligand%20of%20Ate1%20is%20intrinsically%20disordered%20and%20participates%20in%20nucleolar%20phase%20separation%20regulated%20by%20Jumonji%20Domain%20Containing%206&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Arva,%20Akshaya&rft.date=2021-01-05&rft.volume=118&rft.issue=1&rft.spage=1&rft.epage=11&rft.pages=1-11&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2015887118&rft_dat=%3Cjstor_pubme%3E27006438%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2473428466&rft_id=info:pmid/33443146&rft_jstor_id=27006438&rfr_iscdi=true