Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
Abstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/thre...
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2018-02-01
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doaj-937f5fb63a0a43d4a7328c608d9245072020-12-08T03:55:44ZengNature Publishing GroupScientific Reports2045-23222018-02-018111210.1038/s41598-018-21828-6Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZPrem Khanal0Zongchao Jia1Xiaolong Yang2Department of Pathology and Molecular Medicine, Queen’s UniversityDepartment of Biomedical and Molecular Sciences, Queen’s UniversityDepartment of Pathology and Molecular Medicine, Queen’s UniversityAbstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization. Here we provide the first evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer in vitro and in vivo by forming disulphide bond through cysteine residue(s). We have also shown that the homodimers of YAP2L/TAZ are more stable and showed more oncogenic behaviour than their corresponding monomers as revealed by colony formation and cell transformation assay. Since cysteine post-translational regulation plays important roles in redox signalling, tumorigenesis and drug resistance, further studies on the functional effect of this dimerization through post-translational modulation of cysteine residues in YAP2L/TAZ will provide a significant contribution to our understanding of the roles of YAP2L/TAZ in cancer development and therapy.https://doi.org/10.1038/s41598-018-21828-6 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Prem Khanal Zongchao Jia Xiaolong Yang |
spellingShingle |
Prem Khanal Zongchao Jia Xiaolong Yang Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ Scientific Reports |
author_facet |
Prem Khanal Zongchao Jia Xiaolong Yang |
author_sort |
Prem Khanal |
title |
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ |
title_short |
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ |
title_full |
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ |
title_fullStr |
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ |
title_full_unstemmed |
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ |
title_sort |
cysteine residues are essential for dimerization of hippo pathway components yap2l and taz |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-02-01 |
description |
Abstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization. Here we provide the first evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer in vitro and in vivo by forming disulphide bond through cysteine residue(s). We have also shown that the homodimers of YAP2L/TAZ are more stable and showed more oncogenic behaviour than their corresponding monomers as revealed by colony formation and cell transformation assay. Since cysteine post-translational regulation plays important roles in redox signalling, tumorigenesis and drug resistance, further studies on the functional effect of this dimerization through post-translational modulation of cysteine residues in YAP2L/TAZ will provide a significant contribution to our understanding of the roles of YAP2L/TAZ in cancer development and therapy. |
url |
https://doi.org/10.1038/s41598-018-21828-6 |
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