DUSP

DUSP stands for dual specificity phosphatase, a family of protein tyrosine phosphatases that remove phosphate groups from both phosphotyrosine and phosphoserine/threonine residues on substrates. The family is best known for its role in regulating mitogen-activated protein kinase (MAPK) signaling, including ERK, JNK, and p38 pathways, thereby influencing cellular responses to growth factors, stress, and cytokines. DUSPs typically act as negative feedback regulators that modulate the amplitude and duration of MAPK signaling.

Structurally, DUSPs share a conserved catalytic domain belonging to the protein tyrosine phosphatase superfamily, characterized by the HCX5R motif. Many members also contain noncatalytic regions that govern subcellular localization and substrate preference, resulting in nuclear or cytoplasmic distribution and distinct MAPK specificities. Some DUSPs exhibit greater activity toward particular MAPKs (for example, ERK-preferring versus JNK/p38-preferring enzymes), while others display broader activity.

Notable members include DUSP1 (also known as MKP-1), DUSP5, DUSP6 (MKP-3), and DUSP4, among others. The DUSP family is diverse, with individual enzymes differing in expression patterns, inducibility, and regulatory mechanisms. DUSPs can be regulated at the transcriptional level by stimuli that activate MAPK pathways, as well as by post-translational modifications and changes in protein stability.

Clinical relevance of DUSPs arises from their involvement in human diseases. Dysregulated DUSP activity has been linked to cancer, inflammatory and autoimmune disorders, metabolic conditions, and neurodegenerative diseases. Because they shape MAPK signaling, DUSPs are investigated as potential therapeutic targets, and research continues to explore selective modulators and the consequences of altering DUSP function in disease contexts.