COP1 Acts as a Ubiquitin Ligase for PCDH9 Ubiquitination and Degradation in Human Glioma

Constitutive photomorphogenic 1 (COP1, also known as RFWD2), a ring-finger-type E3 ubiquitin ligase, has been reported to play a pivotal role in the regulation of cell growth, apoptosis, and DNA repair. Accumulating evidence has suggested that COP1 plays a role in tumorigenesis by triggering the ubi...

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Published in:Molecular neurobiology 2022-04, Vol.59 (4), p.2378-2388
Main Authors: Zhou, Kunlin, Wang, Lei, Sun, Zhiyuan, Liu, Yuelin, Zhu, Yufu, Liu, Zhiyi, Zhang, Bin, Shi, Hengliang
Format: Article
Language:English
Subjects:
Apoptosis
Biomedical and Life Sciences
Biomedicine
Cadherins - metabolism
Cell Biology
COP1 protein
Degradation
DNA repair
Glioma
Glioma cells
Humans
Neurobiology
Neurology
Neurosciences
Proteasome Endopeptidase Complex - metabolism
Proteasomes
Proteins
Protocadherin
Protocadherins
Tumorigenesis
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - metabolism
Ubiquitination
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Summary:Constitutive photomorphogenic 1 (COP1, also known as RFWD2), a ring-finger-type E3 ubiquitin ligase, has been reported to play a pivotal role in the regulation of cell growth, apoptosis, and DNA repair. Accumulating evidence has suggested that COP1 plays a role in tumorigenesis by triggering the ubiquitination and degradation of its substrates, but the potential mechanism remains unclear. In this study, COP1 was used as a bait in a yeast two-hybrid experiment to screen COP1-interacting proteins in a human brain cDNA library, and the results indicated that protocadherin 9 (PCDH9) was a potential binding protein of COP1. The interaction between and colocalization of COP1 and PCDH9 was further confirmed by coimmunoprecipitation (co-IP) assay and immunofluorescent staining. Subsequently, we demonstrated that COP1 acted as an E3 ligase to promote the ubiquitination and degradation of PCDH9 through the proteasome pathway in glioma cells. Furthermore, we identified that the type of COP1 mediated PCDH9 ubiquitination was Lys 48 -linked polyubiquitination. Finally, we found that the COP1 protein level was inversely correlated with the PCDH9 protein level in human glioma tissues. Taken together, our results suggest that COP1 is an E3 ubiquitin ligase for PCDH9 and reveal an important mechanism for PCDH9 regulation in human glioma.
ISSN:0893-7648
1559-1182
DOI:10.1007/s12035-021-02634-0