Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas

Pit-1 (POU1F1) is a POU-homeodomain transcription factor, and it is one of the most important tissue-specific transcription factors in pituitary development. Cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism under which CDK5...

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Autores principales:	Xie Weiyan, Fang Qiuyue, Guo Jing, Gong Lei, Li Chuzhong, Zhang Yazhuo
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	pit-1 cdk5 prolactinoma phosphorylation proliferation Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c899c81e21fd48509122fb156196d24a
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spelling	oai:doaj.org-article:c899c81e21fd48509122fb156196d24a2021-12-05T14:10:44ZPhosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas2391-542010.1515/chem-2021-0070https://doaj.org/article/c899c81e21fd48509122fb156196d24a2021-07-01T00:00:00Zhttps://doi.org/10.1515/chem-2021-0070https://doaj.org/toc/2391-5420Pit-1 (POU1F1) is a POU-homeodomain transcription factor, and it is one of the most important tissue-specific transcription factors in pituitary development. Cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism under which CDK5 phosphorylates Pit-1 is unclear. To investigate whether CDK5 can regulate cell proliferation and promote hormone secretion through phosphorylation of Ser126-Pit-1 in prolactinomas, we generated an antibody that specifically recognizes phosphorylated serine at position 126 of Pit-1 (Ser126-Pit-1). We used western blotting to detect the level of Pit-1 phosphorylation and observed the proliferation and apoptosis of GH3 cells with different levels of Pit-1 phosphorylation by clone formation experiments, cell viability assays, and flow cytometry. ELISA was used to measure the level of PRL in the supernatant of GH3 cells. Tissue microarrays and immunohistochemistry were used to evaluate the expression of the phosphorylation level of Ser126-Pit-1 (pSer126-Pit-1) in prolactinomas. Our data indicated that Ser126-Pit-1 is specifically phosphorylated by CDK5 and high-level pSer-126-Pit-1 can promote cell proliferation and PRL secretion. In addition, a higher level of pSer-126-Pit-1 correlates with a worse prognosis in patients with prolactinoma. Our results show that CDK5 mediated Ser126-Pit-1 phosphorylation and regulated prolactinoma progression and PRL secretion.Xie WeiyanFang QiuyueGuo JingGong LeiLi ChuzhongZhang YazhuoDe Gruyterarticlepit-1cdk5prolactinomaphosphorylationproliferationChemistryQD1-999ENOpen Chemistry, Vol 19, Iss 1, Pp 785-793 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pit-1 cdk5 prolactinoma phosphorylation proliferation Chemistry QD1-999
spellingShingle	pit-1 cdk5 prolactinoma phosphorylation proliferation Chemistry QD1-999 Xie Weiyan Fang Qiuyue Guo Jing Gong Lei Li Chuzhong Zhang Yazhuo Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
description	Pit-1 (POU1F1) is a POU-homeodomain transcription factor, and it is one of the most important tissue-specific transcription factors in pituitary development. Cyclin-dependent kinase 5 (CDK5) is a protein kinase that can phosphorylate many key transcription factors, but the mechanism under which CDK5 phosphorylates Pit-1 is unclear. To investigate whether CDK5 can regulate cell proliferation and promote hormone secretion through phosphorylation of Ser126-Pit-1 in prolactinomas, we generated an antibody that specifically recognizes phosphorylated serine at position 126 of Pit-1 (Ser126-Pit-1). We used western blotting to detect the level of Pit-1 phosphorylation and observed the proliferation and apoptosis of GH3 cells with different levels of Pit-1 phosphorylation by clone formation experiments, cell viability assays, and flow cytometry. ELISA was used to measure the level of PRL in the supernatant of GH3 cells. Tissue microarrays and immunohistochemistry were used to evaluate the expression of the phosphorylation level of Ser126-Pit-1 (pSer126-Pit-1) in prolactinomas. Our data indicated that Ser126-Pit-1 is specifically phosphorylated by CDK5 and high-level pSer-126-Pit-1 can promote cell proliferation and PRL secretion. In addition, a higher level of pSer-126-Pit-1 correlates with a worse prognosis in patients with prolactinoma. Our results show that CDK5 mediated Ser126-Pit-1 phosphorylation and regulated prolactinoma progression and PRL secretion.
format	article
author	Xie Weiyan Fang Qiuyue Guo Jing Gong Lei Li Chuzhong Zhang Yazhuo
author_facet	Xie Weiyan Fang Qiuyue Guo Jing Gong Lei Li Chuzhong Zhang Yazhuo
author_sort	Xie Weiyan
title	Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
title_short	Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
title_full	Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
title_fullStr	Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
title_full_unstemmed	Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
title_sort	phosphorylation of pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/c899c81e21fd48509122fb156196d24a
work_keys_str_mv	AT xieweiyan phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas AT fangqiuyue phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas AT guojing phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas AT gonglei phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas AT lichuzhong phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas AT zhangyazhuo phosphorylationofpit1bycyclindependentkinase5atserine126isassociatedwithcellproliferationandpoorprognosisinprolactinomas
_version_	1718371807913836544

Phosphorylation of Pit-1 by cyclin-dependent kinase 5 at serine 126 is associated with cell proliferation and poor prognosis in prolactinomas

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