title: Unexpected domain composition of MACC1 links MET signaling and apoptosis.
abstract: Colorectal cancer, one of the most challenging malignancies, still has a limited number of recognized prognostic and predictive markers indicating appropriate treatment. MACC1 (metastasis-associated in colon cancer-1), a novel regulator of tumor growth and metastasis has recently been identified as an important prognostic factor of metastatic disease in colorectal cancer. The mechanism of MACC1 activity remains undetermined. Here we apply a combination of fold recognition and homology modeling algorithms to draft MACC1 function. The applied methods revealed that the MACC1 protein consists of four domains: ZU5, SH3, and two C-terminal death domains (DD). Previously a similar domain architecture (ZU5-DD) was observed in other proteins, involved mainly in signal transduction and apoptosis regulation. Based on the specific aspects of the closest homologues' biology functional hypotheses on MACC1 are proposed. A broad range of bioinformatic analyzes indicates that MACC1, besides its involvement in signal transduction from the MET receptor, links MET signaling and apoptosis.
authors.affiliation: Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kokoszyńska
authors.forename: Jacek
authors.initials: J
authors.lastname: Kryński
authors.forename: Leszek
authors.initials: L
authors.lastname: Rychlewski
authors.forename: Lucjan S
authors.initials: LS
authors.lastname: Wyrwicz
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*
chemical_list: C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D019859:Proto-Oncogene Proteins c-met