is a multidomain tumour suppressor protein involved in the regulation of various cellular processes, such as cell adhesion, migration or proliferation[1]. It is expressed in plethora of organs and tissues, e. g. cerebral cortex, bronchi or the gastrointestinal tract[2]. Germline truncation mutations of APC result in familial adenomatous polyposis, a hereditary form of colon cancer[3]. Additionally, loss of the C-terminal portion of APC is detected in about 80 % of sporadic colon cancers[4].
The overall structure of APC
A schematic of the APC protein domain structure. MCR, mutation cluster region; SAMP, Axin-binding motif
The APC protein, its primary sequence encompassing 2843 aminoacids[5], consists of multiple domains, which enable it to interact with diverse partners. At the N-terminus, an oligomerisation domain is found, enabling the APC protein to oligomerise. It is followed by seven so called armadillo repeats, which form a groove for binding of a guanine nucleotide exchange factor Asef[6]. The central part of APC contains three 15 aminoacid long repeats followed by seven 20 aminoacid long repeats[1]. These motifs serve as binding sites for β-catenin[7]. In between the 20 aminoacid repeats, three SAMP regions are dispersed, enabling the interaction with Axin[1]. At the C-terminus, a basic domain responsible for binding to microtubules as well as EB1 interaction domain are present[8][1].
Interestingly, majority of somatic mutations occurs in so called mutation cluster region (MCR) between codons 1286 and 1513 [9].
Disease
Relevance
Structural highlights
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