Dual specificity protein phosphatase 16 (DUSP16)

Dual specificity protein phosphatase 16 (DUSP16) is an enzyme encoded by the DUSP16 gene and belongs to the dual specificity phosphatase family, which dephosphorylates both phosphoserine/threonine and phosphotyrosine residues on target kinases[1][2][3]. Its primary substrates are the stress-activated mitogen-activated protein kinases (MAPKs) JNK and p38, with weaker activity against ERK[3][4]. DUSP16 acts as a negative regulator of MAPK signaling, attenuating pathways involved in cell cycle progression, differentiation, apoptosis, and response to stress[1][2][3]. High DUSP16 expression is associated with intrinsic resistance to multiple chemotherapeutic agents in several cancer types, acting through suppression of JNK- and p38-mediated pro-apoptotic pathways[4]. Knockdown of DUSP16 sensitizes cancer cells to chemotherapy, and its expression correlates with poor prognosis and chemoresistance in cancers such as nasopharyngeal carcinoma, colorectal, gastric, and breast cancer[4]. DUSP16 is also involved in immune regulation and has been implicated in other diseases including dystonia and epilepsy[2][3]. It is considered a therapeutic target for overcoming chemoresistance, and its expression is a potential biomarker for predicting chemotherapy response[4].

Other names

Dual specificity phosphatase 16KIAA1700MKP7MAP kinase phosphatase 7MAPK phosphatase-7mitogen-activated protein kinase phosphatase 7MKP-7

Modulation of cell sensitivity to chemotherapy via dephosphorylation (and inactivation) of JNK and p38 MAPK, decreasing BAX-mediated apoptosis[4]. Drugs that decrease DUSP16 expression or activity may sensitize cancer cells to chemotherapy; conversely, high DUSP16 activity confers resistance[4].