An activation domain within the walleye dermal sarcoma virus retroviral cyclin protein is essential for inhibition of the viral promoter.
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.
Rovnak
Joel
J
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Hronek
Brett W
BW
Ryan
Sean O
SO
Cai
Sumin
S
Quackenbush
Sandra L
SL
D000595:Amino Acid Sequence; D015536:Down-Regulation; D030283:Epsilonretrovirus / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D012191:Retroviridae Proteins; D014157:Transcription Factors