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Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation

Central precocious puberty (CPP) is attributed to the disorder of some trigger factors those can activate the hypothalamic-pituitary-gonadal axis controlled by GnRH neurons. Many recent studies reveal one of those trigger factors, Makorin ring finger protein 3 (Mkrn3), whose loss-of-function mutatio...

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Autores principales: Liu, Huifang, Kong, Xiangxin, Chen, Fengling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689596/
https://www.ncbi.nlm.nih.gov/pubmed/29156706
http://dx.doi.org/10.18632/oncotarget.19347
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author Liu, Huifang
Kong, Xiangxin
Chen, Fengling
author_facet Liu, Huifang
Kong, Xiangxin
Chen, Fengling
author_sort Liu, Huifang
collection PubMed
description Central precocious puberty (CPP) is attributed to the disorder of some trigger factors those can activate the hypothalamic-pituitary-gonadal axis controlled by GnRH neurons. Many recent studies reveal one of those trigger factors, Makorin ring finger protein 3 (Mkrn3), whose loss-of-function mutations are implicated in CPP. Although Mkrn3 contained zinc Ring finger domain is considered as a putative E3 ubiquitin ligase, its actual function is never reported. Here, our results demonstrated that in mice hypothalamus before and when puberty initiated, Mkrn3 expressed the reversed tendency with Nptx1, which is an important secreted protein for neuron development. Furthermore, our data manifested that Mkrn3 interacted and suppressed Nptx1 activity. And the Ring finger domain of Mkrn3 contained was determined to be essential for binding with Nptx1 for its polyubiquitination during the puberty initiation. Our study shed light on the molecular insights into the function of Mkrn3 in the events of puberty initiation.
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spelling pubmed-56895962017-11-17 Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation Liu, Huifang Kong, Xiangxin Chen, Fengling Oncotarget Research Paper Central precocious puberty (CPP) is attributed to the disorder of some trigger factors those can activate the hypothalamic-pituitary-gonadal axis controlled by GnRH neurons. Many recent studies reveal one of those trigger factors, Makorin ring finger protein 3 (Mkrn3), whose loss-of-function mutations are implicated in CPP. Although Mkrn3 contained zinc Ring finger domain is considered as a putative E3 ubiquitin ligase, its actual function is never reported. Here, our results demonstrated that in mice hypothalamus before and when puberty initiated, Mkrn3 expressed the reversed tendency with Nptx1, which is an important secreted protein for neuron development. Furthermore, our data manifested that Mkrn3 interacted and suppressed Nptx1 activity. And the Ring finger domain of Mkrn3 contained was determined to be essential for binding with Nptx1 for its polyubiquitination during the puberty initiation. Our study shed light on the molecular insights into the function of Mkrn3 in the events of puberty initiation. Impact Journals LLC 2017-07-18 /pmc/articles/PMC5689596/ /pubmed/29156706 http://dx.doi.org/10.18632/oncotarget.19347 Text en Copyright: © 2017 Liu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Huifang
Kong, Xiangxin
Chen, Fengling
Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title_full Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title_fullStr Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title_full_unstemmed Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title_short Mkrn3 functions as a novel ubiquitin E3 ligase to inhibit Nptx1 during puberty initiation
title_sort mkrn3 functions as a novel ubiquitin e3 ligase to inhibit nptx1 during puberty initiation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689596/
https://www.ncbi.nlm.nih.gov/pubmed/29156706
http://dx.doi.org/10.18632/oncotarget.19347
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