Characterization of an Immortalizing N-terminal Domain of Polyomavirus Large T Antigen

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1994 Feb 1

PMID 8289370

Citations 18

Authors

P S Holman

O V Gjoerup

T Davin

B S Schaffhausen

Affiliations

Soon will be listed here.

Abstract

Polyomavirus large T antigen has an N-terminal domain of approximately 260 amino acids which can immortalize primary cells but lacks sequences known to be required for DNA binding and replication. Treatment of full-length large T with either V8 protease or chymotrypsin yields an N-terminal fragment of 36 to 40 kDa and a C-terminal fragment of approximately 60 kDa. This finding suggests a division of the protein into two domains. Proteolysis experiments show that the N-terminal domain does not have strong physical association with the rest of the protein. It also does not self-associate. A construct expressing only the N-terminal 259 amino acids is sufficient for immortalization. The independently expressed N-terminal domain is multiply phosphorylated, although at a lower level than the same region in full-length large T. The 259-residue protein binds to both pRb and p107 with somewhat lower efficiency than the full-length protein.

Citing Articles

A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling.

Denis D, Rouleau C, Schaffhausen B J Virol. 2016; 91(2).

PMID: 27852846 PMC: 5215327. DOI: 10.1128/JVI.01774-16.

Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP.

Rouleau C, Pores Fernando A, Hwang J, Faure N, Jiang T, White E J Virol. 2016; 90(16):7032-7045.

PMID: 27194756 PMC: 4984622. DOI: 10.1128/JVI.00417-16.

JC virus: an oncogenic virus in animals and humans?.

Maginnis M, Atwood W Semin Cancer Biol. 2009; 19(4):261-9.

PMID: 19505654 PMC: 2694964. DOI: 10.1016/j.semcancer.2009.02.013.

Polyomavirus middle T antigen induces the transcription of osteopontin, a gene important for the migration of transformed cells.

Whalen K, Weber G, Benjamin T, Schaffhausen B J Virol. 2008; 82(10):4946-54.

PMID: 18337582 PMC: 2346735. DOI: 10.1128/JVI.02650-07.

Genetic analysis of the polyomavirus DnaJ domain.

Whalen K, De Jesus R, Kean J, Schaffhausen B J Virol. 2005; 79(15):9982-90.

PMID: 16014958 PMC: 1181550. DOI: 10.1128/JVI.79.15.9982-9990.2005.

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