title: A-type lamin-dependent homo-oligomerization for pY19-Caveolin-2 to function as an insulin-response epigenetic regulator.
abstract: Association of Caveolin-2 in the inner nuclear membrane specifically with A-type lamin is crucial for the maintenance of its Tyr-19 phosphorylation to promote insulin-response epigenetic activation at the nuclear periphery. Here, we identify that pY19-Caveolin-2 in the inner nuclear membrane exists as homo-oligomeric forms and the A-type lamin is required for sustenance of its oligomeric status. Oligomerization-defective and hence pY19-dephosphorylated monomeric Caveolin-2 in the inner nuclear membrane is unable to carry out Caveolin-2-mediated epigenetic activation of Egr-1 and JunB genes and transactivation of Elk-1 and STAT3 in response to insulin. The homo-oligomeric pY19-Caveolin-2 localizes in and recruits epigenetic modifiers to the A-type lamin-enriched inner nuclear membrane microdomain for the epigenetic activation. Our data show that A-type lamin-dependent Caveolin-2 homo-oligomerization in the inner nuclear membrane microdomain is a precondition for pY19-Caveolin-2-mediated insulin-response epigenetic activation at the nuclear periphery.
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hayeong
authors.initials: H
authors.lastname: Kwon
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Jaewoong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Kyuho
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Donghwan
authors.initials: D
authors.lastname: Jang
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Moonjeong
authors.initials: M
authors.lastname: Choi
authors.affiliation: Division of Life Science, Graduate School of Applied Life Science (BK21 Plus Program), PMBBRC, Gyeongsang National University, Jinju 660-701, Republic of Korea. Electronic address: ybpak@gnu.ac.kr.
authors.forename: Yunbae
authors.initials: Y
authors.lastname: Pak
mesh_terms: D051243:Caveolin 2 / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014443:Tyrosine; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C495545:Cav2 protein, mouse; D051243:Caveolin 2; C497325:EGR1 protein, human; C494112:ELK1 protein, human; D051766:Early Growth Response Protein 1; D006657:Histones; D007328:Insulin; C581727:JunB protein, human; C494847:LMNA protein, human; D034904:Lamin Type A; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D014443:Tyrosine
keywords: A-type lamin; Caveolin-2; Epigenetic regulators; Homo-oligomerization; Inner nuclear membrane microdomain