Medicina Interna: Acesso Aberto
Acesso livre

Abstrato

Colorectal Cancer: A Pathology of the Colon-Rectum and A Disease of the Genome

Kalakouti Eliana, Lorenzi Federica, Babaei-Jadidi Roya and Nateri S Abdolrahman

Despite the well-established links between signalling and transcriptional activity, little is known about how transcriptional activators are regulated after tumorigenesis is triggered. An obvious mechanism to limit the expression time of an activator is to destroy it via the ubiquitin-proteasome pathway. Ideally, activator turnover should be tied to its efficiency in driving transcription. The F-box protein, FBXW7, is an E3 ubiquitin ligase molecule which targets multiple transcriptional activators and oncoproteins for degradation. FBXW7 mutations occur in nearly 10-15% of human colorectal cancer, making it the fourth most commonly mutated gene after TP53, RAS, and Adenomatous Polyposis Coli (APC). Elucidating its mechanism of action is very important but also difficult as it is likely to influence many pathways due to its role as an E3 ubiquitin ligase in proteasome degradation. Here we attempted to summarize the current state of understanding on this topic.