Purification, cloning and characterization of the pets factor: A nuclear protein that binds to the inducible TG-rich element of the human immunodeficiency virus type 2 enhancer.

Abstract

The pets site (TTGGTCAGGG) of the human immunodeficiency virus type 2 (HIV-2) enhancer mediates induction in activated T cells. Biochemical characterization and purification demonstrate that the dominant protein binding to the pets site is a 43 kd nuclear protein. Using an enriched Southwestern screening technique the 43 kd HIV-2 pets factor was identified as DEK. DEK has previously been shown to be an autoantigen in certain cases of juvenile onset rheumatoid arthritis and to be joined with the C-terminal portion of the nucleoporin protein CAN (nup214) in a fusion protein specific to certain types of acute myelogenous leukemia (AML). This is the first report of a mechanism of action for DEK, which bears little resemblance to other known proteins and contains no previously described DNA-binding motifs. DEK-CAN is an example of the newly described class of fusion oncoproteins, found in AML, which fuse a nuclear DNA-binding protein with a nucleoporin. DEK is further demonstrated to bind to the pets site in the enhancer of troponin-T (TnT), a cellular gene, as well as HIV-2, and is therefore likely to be the first of a new class of DNA-binding/transcription factors.