Transcription factor GATA‐2 is expressed in a number of tissues, including hematopoietic stem and progenitor cells, and is crucial for the proliferation and survival of hematopoietic cells. To further characterize the function of GATA‐2, we examined the cellular turnover mechanism of GATA‐2. In P815 cells, the half‐life of endogenous GATA‐2 was found to be as short as 30 min after cycloheximide treatment. This short half‐life was reproducible in other hematopoietic and neuroblastoma cell lines with moderate variation. We also found that ultraviolet (UV)‐C irradiation markedly represses the GATA‐2 protein level by facilitating the degradation process. Since treatment of the cells with the proteasome inhibitor MG132 or clasto‐Lactacystin substantially abrogated the effects of cycloheximide and UV‐C irradiation and increased the expression level of both endogenous and transfected GATA‐2, the degradation of GATA‐2 seems to occur through the proteasome pathway. Structure‐function analyses with the GAL4‐DNA binding domain (GBD)‐GATA‐2 fusion protein and GATA‐2 deletion mutants suggested that the protein degradation regulatory elements of GATA‐2 reside in three regions, two of which overlap with the transactivation domain. We also detected poly ubiquitinated forms of GATA‐2. Taken together, these results demonstrate that GATA‐2 is turned over rapidly through the ubiquitin‐proteasome pathway.