Dual specificity protein phosphatase 1 (MKP-1) (MKP-1)

Dual specificity protein phosphatase 1 (MKP-1), also known as DUSP1, is a primary negative regulator of the mitogen-activated protein kinase (MAPK) signaling pathways, which are essential for cellular responses to environmental stress and inflammatory stimuli (UniProt P28562). MKP-1 functions by dephosphorylating the critical threonine and tyrosine residues within the activation loops of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK), thereby terminating their signaling activity (PubMed: 28243155). This enzyme is highly inducible by various stimuli, including growth factors, oxidative stress, and glucocorticoids, making it a central component of the cellular feedback loop that prevents excessive inflammation (NIH: PMC3155141). In clinical contexts, MKP-1 is a significant therapeutic target; its induction by glucocorticoids like dexamethasone underlies much of their anti-inflammatory efficacy in treating conditions such as asthma and rheumatoid arthritis (PubMed: 19135141). However, in oncology, MKP-1 is frequently overexpressed and associated with poor prognosis, as it can inhibit the pro-apoptotic signals of JNK and p38, leading to chemoresistance and enhanced tumor cell survival (PubMed: 21149613). Consequently, while inducing MKP-1 is beneficial for inflammatory diseases, developing small-molecule inhibitors like BCI to target MKP-1 is a promising strategy for sensitizing cancer cells to therapy (PubChem CID 2826731).

Other names

DUSP1CL100HVH1PTPN10Mitogen-activated protein kinase phosphatase 1

Dephosphorylation of threonine and tyrosine residues within the activation loop of mitogen-activated protein kinases (MAPKs), specifically p38, JNK, and ERK, leading to their inactivation.