Ubiquitin-Proteasome-Dependent Degradation of GATA-2 and Its Contribution to the UV-C-Induced Down-Regulation.

Transcription factor GATA-2 is crucial for the development of hematopoietic stem cells. GATA-2 regulates proliferation and survival of hematopoietic stem/progenitor cells. We analyzed the degradation process of GATA-2, assuming that GATA-2 may be under the strict controls of protein degradation like many factors regulating cellular proliferations and apoptosis. The half-life of endogenous GATA-2 in hematopoietic and neuroblastoma cells was short (within 30 min in P815 cells) after cycloheximide treatment. The UV-C irradiation also induced the reduction of endogenous GATA-2 expression. Treatment with a proteasome inhibitor MG132 abrogated the effects of cycloheximide and UV-C irradiation, and increased the expression levels of both endogenous and transfected GATA-2 protein. Experiments with GATA-2 deletion mutants and their GBD-fusion proteins revealed that degradation elements of GATA-2 are within the transactivation domains and within a region containing putative protein modification motifs. We detected poly-ubiquitinated forms of GATA-2 after MG132 treatment, implying that the rapid degradation of GATA-2 is ubiquitin-dependent. Together, these results suggest that the ubiquitination/proteasome-dependent degradation pathway regulates the GATA-2 protein expression and this process may be important for the GATA-2 function.