The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation

Abstract

Interaction with SV40 small tumor antigen (small t) compromised the ability of multimeric protein phosphatase 2A to inactivate the mitogen-activated protein kinase ERK1 and the mitogen-activated protein kinase kinase MEK1. Transient expression of small t in CV-1 cells activated MEK and ERK but did not affect Raf activity. Small t stimulated the growth of quiescent CV-1 cells almost as effectively as did serum. Coexpression of kinase-deficient ERK2 blocked most, but not all, of the proliferation caused by small t. Activation of the mitogen-activated protein kinase pathway and stimulation of cell growth were dependent on the interaction of small t with protein phosphatase 2A. These findings indicate that SV40 small t is capable of inducing cell growth through blockade of protein phosphatase and deregulation of the mitogen-activated protein kinase cascade.

Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen

“…Several lines of evidence suggest that ST perturbs cellular targets that participate in human tumor development (Shenk et al, 1976;Crawford et al, 1978;Choi et al, 1988). The ability of ST to transform human cells requires binding to the abundant serine-threonine protein phosphatase 2A (PP2A) (Yang et al, 1991;Sontag et al, 1993). PP2A is a heterotrimer composed of a conserved catalytic C subunit, a structural A subunit and a regulatory B subunit.…”

Identification of the novel KI Polyomavirus in paranasal and lung tissues

“…The TAg binds the oncosuppressor proteins p53 and pRb, two key regulators of cell cycle progression [Bollag et al, 1989;Cress and Nevins, 1996] inhibiting apoptosis and driving the cell into S phase. The small t antigen interacting with the protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation [Sontag et al, 1993]. This aberrant stimulation of the cell cycle is responsible for oncogenic transformation.…”

Functional interaction between a novel protein phosphatase 2A regulatory subunit, PR59, and the retinoblastoma-related p107 protein

“…First, okadaic acid, a strong inhibitor of PP2A, is a tumor promoting agent (Mumby and Walter, 1993). Furthermore, PP2A is a target of transforming proteins of several DNA tumor viruses (Sontag et al, 1993). SV40 small t antigen and polyoma virus small t and middle T antigens, which have a helper function in transformation, can replace certain B subunits in PP2A complexes.…”

“…SV40 small t antigen and polyoma virus small t and middle T antigens, which have a helper function in transformation, can replace certain B subunits in PP2A complexes. As a result, SV40 small t antigen inhibits the PP2A phosphatase activity towards signal transduction kinases MEK and ERK (Sontag et al, 1993). That there is speci®city in this interference with the activity of PP2A holo-enzymes is illustrated by the ®nding that the variable subunit in PP2A trimeric complexes puri®ed from bovine heart is not replaced by SV40 small t (Kamibayashi and Mumby, 1995).…”