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Title

Targeting the retinoblastoma protein by MC007L, gene product of the molluscum contagiosum virus: detection of a novel virus-cell interaction by a member of the poxviruses

Authors
Mohr, Stefan
Massimi, Paola
Darai, Gholamreza
Banks, Lawrence
Zeier, Martin
Muranyi, Walter
Published in Journal of virology. 2008, vol. 82, no. 21, p. 10625-33
Abstract The human pathogenic poxvirus molluscum contagiosum virus (MCV) is the causative agent of benign neoplasm, with worldwide incidence, characterized by intraepidermal hyperplasia and hypertrophy of cells. Here, we present evidence that the MC007L protein of MCV targets retinoblastoma protein (pRb) via a conserved LxCxE motif, which is present in many viral oncoproteins. The deregulation of the pRb pathway plays a central role in tumor pathogenesis. The oncoproteins of small DNA viruses contain amino acid sequences that bind to and inactivate pRb. Isolated expression of these oncoproteins induces apoptosis, cell proliferation, and cellular transformation. The MC007L gene displays no homology to other genes within the poxvirus family. The protein anchors into the outer mitochondrial membrane via an N-terminal mitochondrial targeting sequence. Through the LxCxE motifs, MC007L induces a cytosolic sequestration of pRb at mitochondrial membranes, leading to the inactivation of the protein by mislocalization. MC007L precipitates the endogenous pRb/E2F-1 complex. Moreover, MC007L is able to cooperate to transform primary rat kidney cells. The interaction between MC007L and pRb provides a novel mechanism by which a virus can perturb the cell cycle.
Keywords Amino Acid MotifsAmino Acid SequenceAnimalsCell LineConserved SequenceHumansMitochondrial Membranes/chemistryMolecular Sequence DataMolluscum contagiosum virus/physiologyOncogene Proteins/metabolismProtein BindingProtein Interaction Domains and MotifsRatsRetinoblastoma Protein/antagonists & inhibitors/metabolismViral Proteins/metabolism
Identifiers
PMID: 18701596
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MOHR, Stefan et al. Targeting the retinoblastoma protein by MC007L, gene product of the molluscum contagiosum virus: detection of a novel virus-cell interaction by a member of the poxviruses. In: Journal of virology, 2008, vol. 82, n° 21, p. 10625-33. https://archive-ouverte.unige.ch/unige:18691

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Deposited on : 2012-03-06

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