The human DNA-activated protein kinase phosphorylates simian virus 40 T antigen at amino- and carboxy-terminal sites.

AUTOR(ES)

Chen, Y R

RESUMO

Protein phosphorylation modulates the functions of simian virus 40 large T antigen (TAg) in productive and transforming infections. We recently described a DNA-activated protein kinase (DNA-PK) that efficiently phosphorylates TAg and several other nuclear, DNA-binding proteins in vitro (S.P. Lees-Miller, Y.-R. Chen, and C. W. Anderson, Mol. Cell. Biol. 10:6472-6481, 1990). In this report, we show by direct amino acid sequence analysis that DNA-PK phosphorylates TAg strongly at Ser-677, a residue known to be important for TAg interaction with origin site I and for transformation. We propose that DNA-PK may modulate the role of TAg in repressing early viral transcription and cell transformation, but a role for DNA-PK in regulating simian virus 40 DNA synthesis is not excluded. DNA-PK also phosphorylates Ser-665, and Ser-667, and one or more serines between amino acids 110 and 131. At least six serines, Ser-111, Ser-112, Ser-120, Ser-665, Ser-667, and Ser-677, are phosphorylated in TAg purified from baculovirus vector-infected insect cells.

Documentos Relacionados

• Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen.
• Biochemical characterization of phosphorylation site mutants of simian virus 40 large T antigen: evidence for interaction between amino- and carboxy-terminal domains.
• Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53.
• The DNA-activated protein kinase is required for the phosphorylation of replication protein A during simian virus 40 DNA replication.
• Phosphorylation of threonine in the proline-rich carboxy-terminal region of simian virus 40 large T antigen.