Poly(ADP-ribose) polymerase family member 14 (PARP14)

Poly(ADP-ribose) polymerase family member 14 (PARP14) is an intracellular enzyme belonging to the macro-type subfamily of poly(ADP-ribose) polymerases. It catalyzes mono‑ADPr transfer from NAD+ onto target proteins—a post-translational modification known as mono‑ADPr ribosylation. Structurally, it contains three macrodomains that bind ADPr with varying affinities, a WWE domain stabilizing its structure via ADPr derivatives binding, RNA recognition motifs, and a catalytic domain responsible for enzymatic activity. Functionally, it acts both as an enzyme modifying substrates post-translationally and as a reader recognizing such modifications. Biologically, it serves key roles in regulating immune responses through STAT signaling pathways (notably enhancing STAT6-dependent transcription), modulating cellular metabolism toward glycolysis typical of cancer cells ("Warburg effect"), supporting cell survival under stress conditions such as those found in tumors or inflammation. High expression has been linked to several cancers including multiple myeloma where it promotes resistance to apoptosis; thus making it an emerging therapeutic target especially where selective inhibition could disrupt tumor growth or restore normal immune balance.

Other names

ARTD8BAL2COAST6

Drugs targeting this molecule generally act by inhibiting mono‑ADP‑ribosylation activity—blocking transfer of ADPr from NAD+ to substrate proteins. They also modulate transcriptional coactivation functions that affect immune signaling pathways, and sensitize cancer cells to apoptosis or anti-cancer agents by disrupting pro-survival signals mediated by JNK2 or metabolic reprogramming.