Viral and cellular factors that target the promyelocytic leukemia oncogenic domains strongly activate a glucocorticoid-responsive promoter.
Promyelocytic leukemia (PML) oncogenic domains (PODs) accumulate the transcriptional cofactor named CREB binding protein (CBP) and have been suggested to function as centers of transcription. Transcriptional activation by nuclear hormones, such as glucocorticoids, is augmented by the key constituent of PODs, the PML protein, and decreased by the POD-associated Tax protein of human T-cell leukemia virus type 1 (HTLV-1). This led to the hypothesis that intact PODs might play a positive role in the activation of these promoters. We report here that transiently expressed E4orf3 protein of adenovirus type 5, immediate-early protein 1 of human cytomegalovirus, and the PML-retinoic acid receptor fusion protein from leukemia cells each redistribute CBP within the nucleus. However, unlike the Tax protein of HTLV-1, these factors did not inhibit a glucocorticoid-inducible promoter but strongly enhanced its activity. Thus, at least glucocorticoid-induced transcription does not depend on POD integrity.
Wienzek
S
S
Institut für Virologie, Philipps-Universität Marburg, 35037 Marburg, Germany.
Dobbelstein
M
M
D000256:Adenoviridae / Q000737:chemistry; D017504:Adenovirus E4 Proteins / Q000235:genetics / Q000502:physiology*; D003587:Cytomegalovirus / Q000737:chemistry; D005938:Glucocorticoids; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000502:physiology*; D000071156:Promyelocytic Leukemia Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins
D017504:Adenovirus E4 Proteins; D005938:Glucocorticoids; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human