Comprehensive analysis of expression pattern and promoter regulation of human autophagy-related genes.

Autophagy is a highly conserved pathway for the degradation and recycling of long-lived proteins and cytoplasmic organelles. Similar to apoptosis, autophagy is a critical regulatory mechanism for determining cellular fate and various pathophysiological conditions in metazoans. So far, the systematic analysis of the expression patterns and transcriptional regulation of autophagy-related (ATG) genes has remained incompletely defined. In this study, we used RT-PCR to analyze the expression patterns of 26 human ATG genes simultaneously using cDNA derived from different adult and fetal tissues. As a result, we observed a characteristic ubiquitous expression pattern for all the genes except for ATG2A, ATG9B, and WIPI2. In particular, ATG2A was the only upregulated gene in the etoposide-induced apoptosis of HeLa cells. ATG2A mRNA was also upregulated by doxorubicin. Furthermore, we demonstrated that 13 out of 23 human ATG gene promoters were regulated by the transcription factor E2F1 in HeLa cells, indicating that these constructs could be useful for examining how the autophagy pathway is involved in other cellular phenomena, such as apoptosis evoked by various stimuli. Taken together, these results suggest that autophagy might be regulated at both the transcriptional level and the post-translational level.