DUSP1

DUSP1, or dual specificity phosphatase 1, also known as MKP-1 (mitogen-activated protein kinase phosphatase-1), is an enzyme encoded by the DUSP1 gene in humans. It belongs to the dual specificity phosphatase family and can remove phosphate groups from both threonine and tyrosine residues on protein substrates.

DUSP1 functions as a negative regulator of the mitogen-activated protein kinase (MAPK) signaling pathways. Its primary substrates are the MAP kinases ERK1/2, JNK, and p38. By dephosphorylating these kinases, DUSP1 dampens MAPK-driven signals, thereby modulating cellular processes such as proliferation, differentiation, apoptosis, and inflammatory responses. The protein is found in both the cytoplasm and nucleus and can shuttle between compartments depending on context.

Expression of DUSP1 is rapidly induced by a variety of stimuli, including cellular stress, pro-inflammatory cytokines, growth factors, and hormones. Transcriptional upregulation is driven by factors such as AP-1, NF-κB, and CREB, and glucocorticoids can also enhance its expression. This rapid inducibility makes DUSP1 a key component of a negative feedback loop that resets MAPK signaling after activation. Post-translational mechanisms, including phosphorylation and ubiquitination, influence its stability and activity.

In health and disease, DUSP1 plays roles in inflammatory and immune responses, neuronal signaling, and cancer biology. Altered DUSP1 expression has been linked to inflammatory diseases and various cancers, where it can influence sensitivity to therapy by modulating MAPK-dependent survival or death signals. Because of its central role in MAPK regulation, DUSP1 is of interest as a potential therapeutic target for conditions involving dysregulated MAPK signaling.