DUSP6

DUSP6 (Dual Specificity Phosphatase 6) is a protein-coding gene that plays a crucial role in regulating cellular signaling pathways. It is a member of the dual-specificity phosphatase (DUSP) family, which is known for its ability to dephosphorylate both tyrosine and serine/threonine residues on target proteins. DUSP6 is primarily involved in the negative regulation of the mitogen-activated protein kinase (MAPK) signaling pathway.

Function

DUSP6 acts as a negative regulator of MAPK signaling by dephosphorylating and inactivating extracellular signal-regulated kinases 1 and 2 (ERK1/2). ERK1/2 are key components of the MAPK pathway and are involved in various cellular processes, including cell proliferation, differentiation, and survival. By dephosphorylating ERK1/2, DUSP6 helps to maintain the balance of MAPK signaling and prevent excessive activation of this pathway.

Role in Development

DUSP6 has been shown to play a critical role in embryonic development. Studies in mice have demonstrated that DUSP6 is essential for proper skeletal development, as its absence leads to skeletal abnormalities and neonatal lethality. DUSP6 is specifically required for the normal development of long bones, such as the femur and tibia, and its loss results in impaired chondrocyte differentiation and endochondral ossification.

Clinical Significance

Aberrant regulation of DUSP6 has been implicated in various human diseases, including cancer. DUSP6 acts as a tumor suppressor in certain types of cancer, such as lung and breast cancer, by negatively regulating the MAPK pathway. Loss of DUSP6 expression or function can lead to sustained activation of ERK1/2 and promote tumor growth and progression.

Crystal structure of DUSP6

Structure

DUSP6 is a cytoplasmic protein that consists of a conserved catalytic domain and a C-terminal non-catalytic domain. The catalytic domain contains the signature dual-specificity phosphatase motif, which is responsible for its phosphatase activity. The non-catalytic domain is involved in protein-protein interactions and may contribute to the regulation of DUSP6 activity.

See Also

• MAPK signaling pathway
• Dual-specificity phosphatase
• ERK1/2
• Chondrocyte differentiation
• Endochondral ossification
• Tumor suppressor
• Lung cancer
• Breast cancer