Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting

H. J. Kwun; J. A. Wendzicki; Y. Shuda; P. S. Moore; Y. Chang

doi:10.1038/onc.2017.277

Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting

H. J. Kwun, J. A. Wendzicki, Y. Shuda, P. S. Moore, Y. Chang

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.

Original language	English (US)
Pages (from-to)	6784-6792
Number of pages	9
Journal	Oncogene
Volume	36
Issue number	49
DOIs	https://doi.org/10.1038/onc.2017.277
State	Published - 2017

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

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10.1038/onc.2017.277

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title = "Merkel cell polyomavirus small T antigen induces genome instability by E3 ubiquitin ligase targeting",

abstract = "The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.",

author = "Kwun, {H. J.} and Wendzicki, {J. A.} and Y. Shuda and Moore, {P. S.} and Y. Chang",

note = "Funding Information: We thank Gutian Xiao for providing the HA-βTrCP plasmid, Bert Vogelstein for providing the HCT116 cells, and Megan Lambert and Robin Frederick for assistance in mouse studies, and Meredith Monk for help with the manuscript. The cytogenetic analyses were performed in the Cytogenomics Shared Resource at the University of Minnesota with support from the comprehensive Masonic Cancer Center grant P30CA077598. This study was supported by National Institutes of Health (NIH) grants CA136363 and CA120726 to PSM and YC, who are also supported as American Cancer Society Research Professors. Additional support was provided by the NIH grant T32AI049820 to JAW as a predoctoral trainee. This project used the UPCI Animal and Cytometry Facilities that are supported in part by award P30CA047904.",

year = "2017",

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AU - Shuda, Y.

AU - Moore, P. S.

AU - Chang, Y.

N1 - Funding Information: We thank Gutian Xiao for providing the HA-βTrCP plasmid, Bert Vogelstein for providing the HCT116 cells, and Megan Lambert and Robin Frederick for assistance in mouse studies, and Meredith Monk for help with the manuscript. The cytogenetic analyses were performed in the Cytogenomics Shared Resource at the University of Minnesota with support from the comprehensive Masonic Cancer Center grant P30CA077598. This study was supported by National Institutes of Health (NIH) grants CA136363 and CA120726 to PSM and YC, who are also supported as American Cancer Society Research Professors. Additional support was provided by the NIH grant T32AI049820 to JAW as a predoctoral trainee. This project used the UPCI Animal and Cytometry Facilities that are supported in part by award P30CA047904.

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