A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation

Abstract The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function...

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Autores principales:	Saloni Sinha, Venkata Anudeep Bheemsetty, Maneesha S. Inamdar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/24e347694055473281a5c0745a1a2906
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spelling	oai:doaj.org-article:24e347694055473281a5c0745a1a29062021-12-02T12:32:59ZA double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation10.1038/s41598-018-25667-32045-2322https://doaj.org/article/24e347694055473281a5c0745a1a29062018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25667-3https://doaj.org/toc/2045-2322Abstract The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function of OCIAD2 in non-cancerous contexts remains unknown. Here, we report that ociad2 neighbors ociad1/asrij in most vertebrate genomes, and the two genes likely arose by tandem gene duplication, probably somewhere between the Ordovician and Silurian eras. We show that ociad2 expression is higher in the mouse kidney, liver and brain relative to other tissues. OCIAD2 localizes to early endosomes and mitochondria, and interacts with Asrij and STAT3. Knockdown and overexpression studies showed that OCIAD2 is essential for STAT3 activation and cell migration, which could contribute to its role in tumor metastasis. Structure prediction programs, protein disruption studies, biochemical and functional assays revealed a double helical motif in the OCIA domain that is necessary and sufficient for its localization, interactions and STAT3 activation. Given the importance of JAK/STAT signaling in development and disease, our studies shed light on the evolution and conserved function of the OCIA domain in regulating this pathway and will be critical for understanding this clinically important protein family.Saloni SinhaVenkata Anudeep BheemsettyManeesha S. InamdarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Saloni Sinha Venkata Anudeep Bheemsetty Maneesha S. Inamdar A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
description	Abstract The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function of OCIAD2 in non-cancerous contexts remains unknown. Here, we report that ociad2 neighbors ociad1/asrij in most vertebrate genomes, and the two genes likely arose by tandem gene duplication, probably somewhere between the Ordovician and Silurian eras. We show that ociad2 expression is higher in the mouse kidney, liver and brain relative to other tissues. OCIAD2 localizes to early endosomes and mitochondria, and interacts with Asrij and STAT3. Knockdown and overexpression studies showed that OCIAD2 is essential for STAT3 activation and cell migration, which could contribute to its role in tumor metastasis. Structure prediction programs, protein disruption studies, biochemical and functional assays revealed a double helical motif in the OCIA domain that is necessary and sufficient for its localization, interactions and STAT3 activation. Given the importance of JAK/STAT signaling in development and disease, our studies shed light on the evolution and conserved function of the OCIA domain in regulating this pathway and will be critical for understanding this clinically important protein family.
format	article
author	Saloni Sinha Venkata Anudeep Bheemsetty Maneesha S. Inamdar
author_facet	Saloni Sinha Venkata Anudeep Bheemsetty Maneesha S. Inamdar
author_sort	Saloni Sinha
title	A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
title_short	A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
title_full	A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
title_fullStr	A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
title_full_unstemmed	A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
title_sort	double helical motif in ociad2 is essential for its localization, interactions and stat3 activation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/24e347694055473281a5c0745a1a2906
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A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation

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