Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5508694 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2016 | 9 Pages |
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.
Keywords
acH3acetylated histone H3Homo-oligomerizationEpigenetic regulatorsHistone H3 lysine 9 trimethylationH3K9acINMPTP1BQuantitative reverse transcriptionqRTSTAT3histone H3 lysine 9 acetylationCav-2H3K9me3HEKSmall interfering RNAsiRNATSSschromatin immunoprecipitationtranscription start sitesendoplasmic reticulumInner nuclear membranePlasma membranesignal transducer and activator of transcription 3A-type laminwild typeProtein tyrosine phosphatase 1BCHiPCaveolin-2human embryonic kidney
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Authors
Hayeong Kwon, Jaewoong Lee, Kyuho Jeong, Donghwan Jang, Moonjeong Choi, Yunbae Pak,