An activation domain within the walleye dermal sarcoma virus retroviral cyclin protein is essential for inhibition of the viral promoter

Virology. 2005 Nov 25;342(2):240-51. doi: 10.1016/j.virol.2005.08.011. Epub 2005 Sep 15.

Abstract

Walleye dermal sarcoma virus (WDSV) is a complex retrovirus associated with seasonal dermal sarcomas. Developing tumors have low levels of accessory gene transcripts, A1 and B, and regressing tumors have high levels of full-length and spliced transcripts. Transcript A1 encodes a retroviral cyclin (rv-cyclin) with limited homology to host cyclins. The rv-cyclin is physically linked to components of the transcriptional co-activator complex, Mediator, and regulates transcription. In walleye fibroblasts, it inhibits the WDSV promoter independently of cis-acting DNA sequences. The rv-cyclin activates transcription from GAL4 promoters when fused to the GAL4 DNA binding domain. A 30 a.a. activation domain in the carboxy region can be inactivated by single point mutations, and these mutations diminish the ability of the rv-cyclin to inhibit the WDSV promoter. When fused to glutathione S-transferase, the rv-cyclin, its carboxy region, and the activation domain pull down components of transcription complexes from nuclear extracts, and pull down is lost by mutation of the activation domain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Down-Regulation
  • Epsilonretrovirus / chemistry
  • Epsilonretrovirus / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic / physiology*
  • Protein Structure, Tertiary / genetics
  • Retroviridae Proteins / genetics*
  • Retroviridae Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • Retroviridae Proteins
  • Transcription Factors