WTAP and BIRC3 are involved in the posttranscriptional mechanisms that impact on the expression and activity of the human lactonase PON2
The activity of human paraoxonase 2 (PON2) is rapidly reduced in cells incubated with the bacterial quorormone 3-Oxo-dodecanoyl Homoserine Lactone (3OC12HSL), an observation that led to hypothesize a fast PON2 post-translational modification (PTM). Recently, we detected a 3OC12HSL-induced PTM in a c...
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| Veröffentlicht in: | Cell death & disease 2020-05, Vol.11 (5), p.324-324, Article 324 |
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| creator | Carusone, Teresa Maria Cardiero, Giovanna Cerreta, Mariangela Mandrich, Luigi Moran, Oscar Porzio, Elena Catara, Giuliana Lacerra, Giuseppina Manco, Giuseppe |
| description | The activity of human paraoxonase 2 (PON2) is rapidly reduced in cells incubated with the bacterial quorormone 3-Oxo-dodecanoyl Homoserine Lactone (3OC12HSL), an observation that led to hypothesize a fast PON2 post-translational modification (PTM). Recently, we detected a 3OC12HSL-induced PTM in a cell-free system in which a crude extract from 3OC12HSL-treated HeLa cells was able to inactivate and ubiquitinate at position 144 a recombinant PON2. Here we show the occurrence of this and new PTMs on PON2 in HeLa cells. PTMs were found to gather nearby the two SNPs, A148G, and S311C, that are related to type-2 diabetes and its complications. Furthermore, we detected a PTM nearby a 12 amino acids region that is deleted in PON2 Isoform 2. An in vitro mutation analysis showed that the SNPs and the deletion are involved in PON2 activity and suggested a role of PTMs on its modulation, while a SAXS analysis pointed to Isoform 2 as being largely unstructured, compared to the wild type. Besides, we discovered a control of PON2 expression
via
a putative mRNA operon involving the Wilms tumor 1 associated protein (WTAP) and the E3 ubiquitin ligase (E3UbL) baculoviral IAP repeat-containing 3 (BIRC3). |
| doi_str_mv | 10.1038/s41419-020-2504-2 |
| format | Article |
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via
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via
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metabolism</topic><topic>Amino Acid Sequence</topic><topic>Antibodies</topic><topic>Aryldialkylphosphatase - chemistry</topic><topic>Aryldialkylphosphatase - genetics</topic><topic>Aryldialkylphosphatase - metabolism</topic><topic>Baculoviral IAP Repeat-Containing 3 Protein - metabolism</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell-free system</topic><topic>Diabetes mellitus</topic><topic>Gene deletion</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene Silencing</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kinetics</topic><topic>Life Sciences</topic><topic>Models, Biological</topic><topic>Models, Molecular</topic><topic>mRNA</topic><topic>Operon - genetics</topic><topic>Paraoxonase</topic><topic>Peptides - chemistry</topic><topic>Peptides - metabolism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Post-transcription</topic><topic>Post-translation</topic><topic>Protein Isoforms - chemistry</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Processing, Post-Translational</topic><topic>RNA Splicing Factors - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Scattering, Small Angle</topic><topic>Transcription, Genetic</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><topic>Ubiquitination</topic><topic>WT1 protein</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carusone, Teresa Maria</creatorcontrib><creatorcontrib>Cardiero, Giovanna</creatorcontrib><creatorcontrib>Cerreta, Mariangela</creatorcontrib><creatorcontrib>Mandrich, Luigi</creatorcontrib><creatorcontrib>Moran, Oscar</creatorcontrib><creatorcontrib>Porzio, Elena</creatorcontrib><creatorcontrib>Catara, Giuliana</creatorcontrib><creatorcontrib>Lacerra, Giuseppina</creatorcontrib><creatorcontrib>Manco, Giuseppe</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carusone, Teresa Maria</au><au>Cardiero, Giovanna</au><au>Cerreta, Mariangela</au><au>Mandrich, Luigi</au><au>Moran, Oscar</au><au>Porzio, Elena</au><au>Catara, Giuliana</au><au>Lacerra, Giuseppina</au><au>Manco, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>WTAP and BIRC3 are involved in the posttranscriptional mechanisms that impact on the expression and activity of the human lactonase PON2</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2020-05-07</date><risdate>2020</risdate><volume>11</volume><issue>5</issue><spage>324</spage><epage>324</epage><pages>324-324</pages><artnum>324</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>The activity of human paraoxonase 2 (PON2) is rapidly reduced in cells incubated with the bacterial quorormone 3-Oxo-dodecanoyl Homoserine Lactone (3OC12HSL), an observation that led to hypothesize a fast PON2 post-translational modification (PTM). Recently, we detected a 3OC12HSL-induced PTM in a cell-free system in which a crude extract from 3OC12HSL-treated HeLa cells was able to inactivate and ubiquitinate at position 144 a recombinant PON2. Here we show the occurrence of this and new PTMs on PON2 in HeLa cells. PTMs were found to gather nearby the two SNPs, A148G, and S311C, that are related to type-2 diabetes and its complications. Furthermore, we detected a PTM nearby a 12 amino acids region that is deleted in PON2 Isoform 2. An in vitro mutation analysis showed that the SNPs and the deletion are involved in PON2 activity and suggested a role of PTMs on its modulation, while a SAXS analysis pointed to Isoform 2 as being largely unstructured, compared to the wild type. Besides, we discovered a control of PON2 expression
via
a putative mRNA operon involving the Wilms tumor 1 associated protein (WTAP) and the E3 ubiquitin ligase (E3UbL) baculoviral IAP repeat-containing 3 (BIRC3).</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32382056</pmid><doi>10.1038/s41419-020-2504-2</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8018-9752</orcidid><orcidid>https://orcid.org/0000-0001-6191-3952</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 38 38/1 42/70 42/89 631/535/1261 631/80/458/582 631/92/607/1164 82/58 82/80 82/83 96/2 A549 Cells Adenosine Diphosphate Ribose - metabolism Amino Acid Sequence Antibodies Aryldialkylphosphatase - chemistry Aryldialkylphosphatase - genetics Aryldialkylphosphatase - metabolism Baculoviral IAP Repeat-Containing 3 Protein - metabolism Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell Cycle Proteins - metabolism Cell-free system Diabetes mellitus Gene deletion Gene expression Gene Expression Regulation Gene Silencing HeLa Cells Humans Immunology Kinetics Life Sciences Models, Biological Models, Molecular mRNA Operon - genetics Paraoxonase Peptides - chemistry Peptides - metabolism Polymorphism, Single Nucleotide - genetics Post-transcription Post-translation Protein Isoforms - chemistry Protein Isoforms - metabolism Protein Processing, Post-Translational RNA Splicing Factors - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Scattering, Small Angle Transcription, Genetic Ubiquitin Ubiquitin-protein ligase Ubiquitination WT1 protein X-Ray Diffraction |
| title | WTAP and BIRC3 are involved in the posttranscriptional mechanisms that impact on the expression and activity of the human lactonase PON2 |
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