Publication: An internal class III PDZ binding motif in HPV16 E6* protein is required for Dlg degradation activity
1
Issued Date
2021-05-01
Resource Type
ISSN
18728006
03044165
03044165
Other identifier(s)
2-s2.0-85100243583
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochimica et Biophysica Acta - General Subjects. Vol.1865, No.5 (2021)
Suggested Citation
Wareerat Umnajvijit, Jariya Sangthong, Fabien Loison, Kulthida Vaeteewoottacharn, Mathurose Ponglikitmongkol An internal class III PDZ binding motif in HPV16 E6* protein is required for Dlg degradation activity. Biochimica et Biophysica Acta - General Subjects. Vol.1865, No.5 (2021). doi:10.1016/j.bbagen.2021.129850 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/76201
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
An internal class III PDZ binding motif in HPV16 E6* protein is required for Dlg degradation activity
Other Contributor(s)
Abstract
Background: A splice product of the E6 oncoprotein, E6*, is found in cells infected with HPV associated with a high-risk for cervical cancer. Both E6* and E6 promote Dlg degradation, considered a contributing factor for the tumorigenic potential of high-risk HPVs. The full-length E6 utilizes a conserved PDZ binding motif (PBM) at the extreme C-terminus to promote Dlg degradation. In contrast, this PBM is absent in E6*. Methods: We performed western blot analysis, site-directed mutagenesis and co-immunoprecipitation to identify the key elements required for Dlg degradation activity of high-risk HPVE6*, using HPV16E6* as a model. Results: Our data indicate that only one of the two internal putative class III PBMs, located between amino acids 24–27 (HDII) of HPV16E6*, was required to facilitate degradation of Dlg protein. Substitution of the two consensus residues in this region (D25 and I27) to glycine greatly diminished activity. Whereas substitution of the two conserved residues in the putative internal class I PBM (amino acids 16–19) or the second putative class III PBM (amino acids 28–31) was without effect. Interestingly, HPV66E6* which does not promote Dlg degradation can be converted into a form capable of facilitating Dlg degradation through the insertion of nine amino acids (20–28) containing the class III PBM from HPV16E6*. HPV16E6*-induced Dlg degradation appeared independent of E6AP. Conclusions: The internal class III PBM of HPV16E6*I required for Dlg degradation is identified. General significance: This study highlights that a novel class III PBM as the domain responsible for Dlg degradation activity in high-risk HPVE6*.