Adenomatous Polyposis Coli – Wikipedia

The gene Adenomatous Polyposis Coli ( APC ) Coding for a 310 kda protein, present both in the cytoplasm and in the nucleus of colic and extracolical cells. It’s a shuttle-protein , that is, a protein capable of moving between the nucleus and cytoplasm, ownership conferred by the presence of amino acid sequences that codify for nuclear location signals ( NLSs ) and exit signals from the nucleus ( NESs ).

APC is divided into multiple domains which constitute an important joint of complex cellular reporting functions. The N-Terminal site contains an oligomerization domain (capable of forming oligomeri) and a domain armadillo able to tie Asef ( A PC- S timulated guanine nucleotide AND xchange F Actor). The central areas contain the bond region with β-catenine, bond sites for axine and a very important site that negatively modulates the link with β-chatenine. The C-Terminal domain contains a site binding site and a site that binds the DLG oncosuppressor protein.

APC is the fulcrum of the reporting route called wingless/wnt .
The main function of the APC is to modulate the cytoplasmic levels of β-catenine, protein capable of migrating in the nucleus and activating protein transcription complexes called TNA (Transcription of CMYC and CICLINA D1). However, nuclear migration of chain complexes is possible if its cytoplasmic concentration is high enough.
In condition normal , APC is linked to CKI (Caseina Chinasi 1) and GSK3 (glycogen synthesis 3 β-chinasi) (cytoplasmic proteins); This large enzymatic complex is able to phosphorylasted β-catenine which, so marked , is therefore destined for degradation through the proteasome.
If the factor wnt It is linked to its receptor complex, there is inactivation of the chinasic properties related to the APC, with the accumulation of β-catenine that is not destined for the proteasome. This causes cell growth.

Alterations of the APC gene are directly connected with pathological paintings such as the family adenomatous polypostral and colorectal carcinoma. In fact, the APC gene presents a weak point which is the mutation cluster region , area where mutations tend to accumulate. In particular, the mutation can cause the truncation at the level of the Mutation Cluster Region, with the loss of the protein structures overlooking the C-Terminal site, containing domains that modulate the phosphorylation of β-chatenine. APC also represents a junctional node of the cytoskeletal and one of its mutation involves the loss of the structure and cell polarity, so as to justify the remarkable degree of pleomorphism and dysplasia in colorectal carcinomas. The important mutations of the cytoskeleton are also the managers of aneuploidia that occurs with the progression of cell proliferation. In addition, the β-catenine, linking APC and Actin, allows the connection with α-catenine and with γ-catenine, structures that give stability to the e-caderin, a protein that mediates cell-cell adhesion. Subvert the stability of these last mechanisms, causes a loss of the contact inhibition and justifies the invasiveness of carcinoma. For this reason, APC seems to have a role in guaranteeing the correct directionality of the migration of colic cells from the base to the apex of the crypts. In fact, the changed cells tend to accumulate in aberrant proliferating prolifery by constituting the adenomatous polyp, the main condition predisposing the sporadic or secondary colonctal carcinoma to family adenomatous polypos.

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