The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells.

Abstract	Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C(pro) induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within the 5' non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C(pro).
Authors	Paul Lawrence, Elizabeth A Schafer, Elizabeth Rieder
Journal	Virology (Virology) Vol. 425 Issue 1 Pg. 40-52 (Mar 30 2012) ISSN: 1096-0341 [Electronic] United States
PMID	22280896 (Publication Type: Journal Article)
Copyright	Published by Elsevier Inc.
Chemical References	Adaptor Proteins, Signal Transducing Khdrbs1 protein, mouse Nuclear Proteins RNA, Small Interfering RNA-Binding Proteins Viral Proteins Cysteine Endopeptidases 3C Viral Proteases 3C proteases
Topics	3C Viral Proteases Adaptor Proteins, Signal Transducing (chemistry, genetics, metabolism) Amino Acid Sequence Animals Cell Line Cricetinae Cysteine Endopeptidases (metabolism) Cytoplasm (metabolism) Foot-and-Mouth Disease Virus (enzymology, pathogenicity) Kidney (cytology, virology) Molecular Sequence Data Nuclear Proteins (genetics, metabolism) Protein Biosynthesis RNA, Small Interfering (genetics, metabolism) RNA-Binding Proteins (chemistry, genetics, metabolism) Ribosomes (virology) Viral Proteins (metabolism)

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