DNA damage-regulated autophagy modulator 1 (DRAM1)

DNA damage-regulated autophagy modulator 1 (DRAM1) is a multi-pass lysosomal membrane protein and direct target of p53, critically involved in the regulation of autophagy and apoptosis in response to cellular stress and DNA damage. DRAM1 modulates autophagy via promoting lysosomal acidification and protease activation, functions in both canonical and non-canonical (alternative) autophagy pathways, and influences cell fate in a context-dependent manner—acting as a tumor suppressor via p53 mediation but potentially also promoting tumorigenesis depending on cell type and disease context. It regulates apoptosis by interacting with and stabilizing BAX, facilitating proapoptotic signaling through both lysosomal and mitochondrial pathways. DRAM1 also interacts with molecules such as STIM1, perturbing calcium homeostasis and linking ER-lysosome contacts, with implications for neurodegenerative and cardiovascular diseases.

Other names

DNA damage-regulated autophagy modulator protein 1DRAMFLJ11259Damage-regulated autophagy modulatorDRAM1

Drugs targeting DRAM1 induce or modulate autophagy and apoptosis, for example: - Increasing DRAM1 levels stimulates autophagy via lysosomal acidification, promoting cellular degradation processes - Recruitment of proapoptotic proteins (e.g., BAX) to lysosomes, leading to activation of lysosomal and mitochondrial pathways of apoptosis - Regulation of PI3K-Akt-mTOR pathway (inhibition leading to decreased cell proliferation and increased cell death)