Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) (PAPSS1)

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is a vital enzyme that catalyzes the synthesis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which serves as the universal sulfate donor for all sulfation reactions in the human body (UniProt: O43252). The enzyme performs a two-step reaction: first, it converts ATP and inorganic sulfate into adenosine 5'-phosphosulfate (APS), and then it phosphorylates APS to produce PAPS (NCBI Gene: 9061). PAPSS1 is generally expressed ubiquitously and is responsible for maintaining the basal levels of PAPS necessary for the sulfation of hormones, neurotransmitters, and structural components like glycosaminoglycans. In various cancers, including prostate and lung cancer, PAPSS1 is often upregulated, contributing to tumor growth by facilitating the sulfation of signaling molecules and receptors (PubMed: 22430268). Targeting PAPSS1 mRNA using RNA interference (RNAi) or antisense technologies is an emerging area of research aimed at reducing PAPS availability and inhibiting oncogenic pathways. While specific clinical drugs targeting PAPSS1 are not yet available, experimental studies have demonstrated that silencing PAPSS1 can reduce the proliferation of certain cancer cell lines. Potential therapeutic challenges include the risk of systemic sulfate depletion and the need for precise delivery to avoid affecting normal physiological sulfation.

Other names

PAPS synthase 1ATP sulfurylase/APS kinase 1SK1ATPSK1

Inhibition of PAPS biosynthesis via mRNA degradation or translational repression