SMAD4

SMAD4 (SMAD family member 4) is a gene that encodes a protein involved in signal transduction and transcriptional regulation in the TGF-beta signaling pathway. It is a member of the SMAD family of proteins, which are critical mediators of transforming growth factor beta (TGF-β) signaling.

Function

SMAD4 is a tumor suppressor gene that plays a crucial role in the regulation of cell growth and apoptosis. It is involved in the TGF-beta signaling pathway, which is important for cell proliferation, differentiation, and development. SMAD4 forms a complex with other SMAD proteins to translocate to the cell nucleus, where it regulates the expression of target genes.

Clinical significance

Mutations in the SMAD4 gene are associated with several cancers, including pancreatic cancer, colorectal cancer, and juvenile polyposis syndrome. Loss of SMAD4 function can lead to uncontrolled cell growth and tumor development.

Pancreatic cancer

SMAD4 mutations are found in approximately 50% of pancreatic ductal adenocarcinomas. The loss of SMAD4 function is associated with poor prognosis and aggressive tumor behavior.

Colorectal cancer

In colorectal cancer, SMAD4 mutations are less common but still significant. They are often associated with advanced stages of the disease and poor clinical outcomes.

Juvenile polyposis syndrome

SMAD4 mutations are also linked to juvenile polyposis syndrome, a hereditary condition characterized by the development of numerous polyps in the gastrointestinal tract and an increased risk of gastrointestinal cancer.

Interactions

SMAD4 interacts with several other proteins, including:

• SMAD2 and SMAD3, which are receptor-regulated SMADs that form complexes with SMAD4 to mediate TGF-β signaling.
• DNA-binding proteins that help regulate the transcription of target genes.

See also

• TGF-beta signaling pathway
• Tumor suppressor gene
• Signal transduction

External links

• SMAD4 gene - NCBI
• SMAD4 - Genetics Home Reference