SAM domain and HD domain-containing protein 1 (SAMHD1) (SAMHD1)

SAM domain and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that plays a pivotal role in maintaining cellular dNTP homeostasis (UniProt: Q9Y3Z3). By depleting the pool of available dNTPs, SAMHD1 serves as an innate immune restriction factor that inhibits the replication of retroviruses like HIV-1 and certain DNA viruses (PubMed: 21613998). Mutations in the SAMHD1 gene are associated with Aicardi-Goutières syndrome, a condition characterized by chronic inflammation and interferon overproduction (PubMed: 19525956). In the field of oncology, SAMHD1 is a major determinant of sensitivity to nucleoside analog chemotherapies, such as cytarabine, because it enzymatically degrades their active triphosphate forms (PubMed: 28029167). Consequently, SAMHD1 is being investigated as a therapeutic target where its inhibition or degradation could overcome drug resistance in various cancers, particularly acute myeloid leukemia.

Other names

Monocyte protein 5MOP-5Dendritic cell-derived IFNG-induced proteinDCIPSAM domain and HD domain 1

SAMHD1 acts as a dNTPase that hydrolyzes deoxynucleoside triphosphates (dNTPs) into deoxynucleosides and inorganic triphosphate. In oncology, it functions as a resistance factor by degrading the active triphosphate metabolites of nucleoside analog drugs. Therapeutic strategies involve inhibiting SAMHD1 or inducing its degradation to prevent the breakdown of these drugs, thereby enhancing their cytotoxic effects in cancer cells.