Two independent regions of simian virus 40 T antigen increase CBP/p300 levels, alter patterns of cellular histone acetylation, and immortalize primary cells.
J Virol
; 87(24): 13499-509, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24089570
ABSTRACT
Simian virus 40 (SV40) large T antigen (SVT) interferes with normal cell regulation and thus has been used to identify cellular components controlling proliferation and homeostasis. We have previously shown that SVT-mediated transformation requires interaction with the histone acetyltransferases (HATs) CBP/p300 and now report that the ectopic expression of SVT in several cell types in vivo and in vitro results in a significant increase in the steady-state levels of CBP/p300. Furthermore, SVT-expressing cells contain higher levels of acetylated CBP/p300, a modification that has been linked to increased HAT activity. Concomitantly, the acetylation levels of histone residues H3K56 and H4K12 are markedly increased in SVT-expressing cells. Other polyomavirus-encoded large T antigens also increase the levels of CBP/p300 and sustain a rise in the acetylation levels of H3K56 and H4K12. SVT does not affect the transcription of CBP/p300, but rather, alters their overall levels through increasing the loading of CBP/p300 mRNAs onto polysomes. Two distinct regions within SVT, one located in the amino terminus and one in the carboxy terminus, can independently alter both the levels of CBP/p300 and the loading of CBP/p300 transcripts onto polysomes. Within the amino-terminal fragment, a functional J domain is necessary for increasing CBP/p300 and specific histone acetylation levels, as well as for immortalizing primary cells. These studies uncover the action of polyomavirus T antigens on cellular CBP/p300 and suggest that additional mechanisms are used by T antigens to induce cell immortalization and transformation.
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Base de dados:
MEDLINE
Assunto principal:
Histonas
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Transformação Celular Viral
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Antígenos Transformantes de Poliomavirus
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Vírus 40 dos Símios
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Infecções por Polyomavirus
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Proteína de Ligação a CREB
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Proteína p300 Associada a E1A
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos