The gibbon ape leukemia virus is a family of type C retroviruses associated with several distinct hematopoietic malignancies. The Seato strain is associated with granulocytic leukemia. The principal determinant of enhancer activity has been shown to reside in a 22 bp element which interacts with cellular proteins. The gibbon T-cell lymphoma cell line MLA 144 strongly transactivates the GALV-Seato enhancer. Fractionation of MLA 144 extracts by conventional and affinity chromatography allows the separation of the GALV enhancer binding protein complex into 2 components. One of these components interacts strongly with DNA but does not in itself possess full specificity. The second component binds with reduced specificity to DNA, but upon forming a complex with the first component, confers greatly enhanced power to discriminate between different sequences. These proteins are distinct and separable from fos/jun (AP1). However, a minor complex is present in MLA 144 which contains a fos-related antigen (FPA). The two components of the major complex can be independently activated in a cell-line specific manner. The first component of the complex has been identified as a modified form of the jun-d protein. The modification, thus far detected only in T- cells, causes the mobility of the jun-d to increase both in SDS- polyacrylamide gels and in DNA binding electrophoretic mobility shift assays. The nature of the modification is under investigation. In addition, it appears that a population of jun-d exists in T-cells which is relatively inactive with the GALV-AP1 site. Modified jun-d, but not recombinant jun-d interacts with a second component, a protein of approximately 20,000 MW, which augments binding to AP1 sites. Importantly this second protein, termed activator, may play an important role in T- cell activation, as it is a component of NFAT (nuclear factor of activated cells) critical for IL-2 induction.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009168-06
Application #
3774370
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code