DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication
| Autor: | Karen P. Mullane, Kathryn S. Campbell, Juan Zalvide, James A. DeCaprio, Brian Schaffhausen, James M. Pipas, Pamela A. Silver, Thomas M. Roberts, I A Aksoy, Hilde Stubdal |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
DNA Replication
Antigens Polyomavirus Transforming Recombinant Fusion Proteins Molecular Sequence Data Eukaryotic DNA replication Simian virus 40 Virus Replication DNAJ Protein Cell Line DNA replication factor CDT1 Replication factor C SeqA protein domain Control of chromosome duplication Genetics Animals Humans HSP70 Heat-Shock Proteins Amino Acid Sequence Heat-Shock Proteins DNA Primers Base Sequence Molecular Structure Sequence Homology Amino Acid biology Escherichia coli Proteins HSC70 Heat-Shock Proteins DNA replication HSP40 Heat-Shock Proteins Mutation biology.protein Origin recognition complex Carrier Proteins Developmental Biology |
| Zdroj: | Genes & Development. 11:1098-1110 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.11.9.1098 |
| Popis: | The amino-terminal domain of SV40 large tumor antigen (TAg) is required for efficient viral DNA replication. However, the biochemical activity associated with this domain has remained obscure. We show here that the amino-terminal domain of TAg shares functional homology with the J-domain of DnaJ/hsp40 molecular chaperones. DnaJ proteins function as cofactors by regulating the activity of a member of the 70-kD heat shock protein family. Genetic analyses demonstrated that amino-terminal sequences of TAg comprise a novel J-domain that mediates a specific interaction with the constitutively expressed hsc70 and show that the J-domain is also required for efficient viral DNA replication in vivo. Furthermore, we demonstrated that the J-domain of two human DnaJ homologs, HSJ1 or DNAJ2, could substitute functionally for the amino-terminus of TAg in promoting viral DNA replication. Together, our findings suggest that TAg uses its J-domain to support SV40 DNA replication in a manner that is strikingly similar to the use of Escherichia coli DnaJ by bacteriophage lambda in DNA replication. However, TAg has evolved a more efficient strategy of DNA replication through an intrinsic J-domain to associate directly with a partner chaperone protein. Our observations provide evidence of a role for chaperone proteins in the process of eukaryotic DNA replication. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|