Human T-cell leukemia virus type 1 Tax transactivates the human proliferating cell nuclear antigen promoter.
The human T-cell leukemia virus type 1 (HTLV-1) transforming protein, Tax, is a potent transactivator of both viral and cellular gene expression. The ability of Tax to transform cells is believed to depend on its transactivation of cellular-growth-regulatory genes. Expression of proliferating cell nuclear antigen (PCNA) is intimately linked to cell growth and DNA replication and repair. By testing a series of PCNA promoter deletion constructs, we have demonstrated that the PCNA promoter can be transactivated by Tax. The smallest construct that was activated did not include the ATF/CRE binding site at nucleotide -50, and mutations in the ATF/CRE element in the context of a larger promoter were still activated by Tax. In addition, a Tax mutant that is defective for activation of the CRE pathway retained the ability to activate the -397 promoter construct. When a series of linker scanner mutations that span the region from nucleotide -45 to -7 were assayed, mutations in and around a repeat sequence were found to abolish Tax transactivation. Multimerized copies of either half of the repeat were Tax responsive. A single protein complex was shown to bind specifically to the Tax-responsive region, and the binding of this complex was enhanced in the presence of Tax. These results demonstrate that the PCNA promoter contains a Tax-responsive element located between nucleotides -45 and -7 whose sequence is different from those of other, previously identified Tax-responsive elements. The ability of Tax to activate the PCNA promoter may play an important role in cellular transformation by HTLV-1.
Ressler
S
S
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Morris
G F
GF
Marriott
S J
SJ
D001483:Base Sequence; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000235:genetics*; D015490:HTLV-I Infections / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D016356:Gene Products, tax; D018809:Proliferating Cell Nuclear Antigen