HD domain-containing protein 3 (HDDC3)

HD domain-containing protein 3 (HDDC3), also known as MESH1 (Metazoan SpoT homolog 1), is a cytosolic enzyme homologous to the bacterial SpoT hydrolase, with known activity as a guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase ((ppGpp)ase)[2][3][8]. It contributes to the regulation of the cellular response to nutrient starvation and plays a key role in regulating NADPH levels and dNTP pool synthesis in mammalian cells[1][2][3][8]. In humans, depletion or inhibition of HDDC3/MESH1 leads to proliferation arrest in cancer cells, depletion of dNTPs, repression of key proliferative transcriptional regulators (like TAZ), and protection against ferroptosis, indicating its potential as a therapeutic target in oncology[1][2]. HDDC3 is associated with chromatin modifications and cellular stress response pathways, and its higher expression is linked to cancer progression and poor clinical outcomes[1][3]. There is no known approved drug targeting HDDC3, but its central role in proliferation and metabolic adaptation identifies it as a candidate for novel therapeutic interventions[1][2].

Other names

Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1MESH1(ppGpp)aseMetazoan SpoT homolog 1Penta-phosphate guanosine-3'-pyrophosphohydrolaseHD domain containing 3HD domain-containing protein 3MGC45386MYNRL15Myeloid leukemia noncoding regulatory locus on chromosome 15

Enzymatic hydrolysis of (p)ppGpp and regulation of metabolic stress pathways[3][8]\nRegulation of cell proliferation via epigenetic repression of TAZ expression[1]\nRegulation of NADPH levels and ferroptosis susceptibility[2]