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Basic Characteristics of Mutations
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Mutation Site
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L142A |
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Mutation Site Sentence
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Both sT and sT.L142A increased c-Myc expression and prolonged its turnover, an effect which is lost for sT.LSD91-95A. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Small T |
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Standardized Encoding Gene
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MCPyV_gp4
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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FBXW7
MYC
CCNE1
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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23954152
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Title
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Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7
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Author
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Kwun HJ,Shuda M,Feng H,Camacho CJ,Moore PS,Chang Y
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Journal
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Cell host & microbe
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Journal Info
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2013 Aug 14;14(2):125-35
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Abstract
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Merkel cell polyomavirus (MCV) causes an aggressive human skin cancer, Merkel cell carcinoma, through expression of small T (sT) and large T (LT) viral oncoproteins. MCV sT is also required for efficient MCV DNA replication by the multifunctional MCV LT helicase protein. We find that LT is targeted for proteasomal degradation by the cellular SCF(Fbw7) E3 ligase, which can be inhibited by sT through its LT-stabilization domain (LSD). Consequently, sT also stabilizes cellular SCF(Fbw7) targets, including the cell-cycle regulators c-Myc and cyclin E. Mutating the sT LSD decreases LT protein levels and eliminates synergism in MCV DNA replication as well as sT-induced cell transformation. SCF(Fbw7) knockdown mimics sT-mediated stabilization of LT, but this knockdown is insufficient to fully reconstitute the transforming activity of a mutant LSD sT protein. Thus, MCV has evolved a regulatory system involving SCF(Fbw7) that controls viral replication but also contributes to host cell transformation.
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Sequence Data
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-
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