In silico analysis of tumor suppressor Smad4 gene / Mahirah Abdul Razak

Smad4 gene is an essential signal transducer of the transforming growth factor β (TGF­ β) signaling pathway and has been identified as a tumor suppressor, being mutated in approximately 30% of colorectal cancers. The human Smad4 gene encodes a 552 amino acid coding sequence, which contains 11 exons and located in chromosome 18q21. Lacking in the signature phosphorylation site in its C terminus, Smad4 is unable to associate with TGF-βR complex. In the nucleus, Smad4 binds to specific short sequences of DNA directly or indirectly and regulate transcription of the targeted genes, leading to the regulation of cellular proliferation. Smad4 protein has two regions that contain highly conserved amino-terminal and carboxyl-terminal, known as Mad homology 1 (MHl) and Mad homology 2 (MH2). Germline mutations in the Smad4 gene have been detected in nearly 25 to 60% of the cases analyzed and 90% of the mutations located in the MH2 region. In CRC, Smad4 gene mutations are found in carcinomas and increased frequencies of metastatic CRC, and these mutations cannot be detected in premalignant stages. In silico identification and characterization of Smad4 provide preliminary information on the structure and function of the gene in human. In addition, comparative modeling is becoming a useful technique in the field of bioinformatics because the knowledge of the three-dimensional structure of protein would be an invaluable aid to understand the details of a particular protein. The predicted three-dimensional model may be further used in characterizing the interest protein in wet laboratory. The methods in this study can be used to get more information about biosystem by identifying and characterization of other genes and biomolecules.