Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in most sporadic colorectal tumors. During both embryonic and postnatal periods, APC is widely expressed in a variety of tissues, including the brain and gastrointestinal tract. The APC gene product (APC) is a large multidomain protein consisting of 2843 amino acids. APC downregulates the Wnt signaling pathway through its binding to beta-catenin and Axin. Most mutated APC proteins in colorectal tumors lack the beta-catenin-binding regions and fail to inhibit Wnt signaling, leading to the overproliferation of tumor cells. Several mouse models (APC580D, APCDelta716, APC1309, APCMin, APC1638T) have been established to investigate carcinogenesis caused by APC mutations. APC also binds to APC-stimulated guanine nucleotide exchange factor, the kinesin superfamily-associated protein 3, IQGAP1, microtubules, EB1, and discs large (DLG). APC has both nuclear localization signals and nuclear export signals in its molecule, suggesting its occasional nuclear localization and export of beta-catenin from the nucleus. APC is highly expressed in the intestinal and colorectal epithelia and may be involved in homeostasis of the enterocyte renewal phenomena, in which proliferation, migration, differentiation, and apoptosis are highly regulated both temporally and spatially. Through the many binding proteins mentioned, APC can exert multiple functions involved in epithelial homeostasis.
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PMID:Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia. 1757 42

Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. The term Gardner's syndrome is used to describe extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive fibromatosis), that are especially prominent in families with FAP. We postulate that a ciliary dysfunction is the underlying pathogenetic mechanism of extraintestinal manifestations in patients with FAP. This postulation is based on the presence of common clinical manifestations (ie, cysts, retinal abnormalities, and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally, both APC and the cilia have degradation of beta-catenin as the common downstream target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin. Proofs of principle that beta-catenin could be the key mediator of the ciliary disorder also rely in the findings that overexpression of beta-catenin induces polycystic kidney disease, and CHRPE phenotypes in animal models. Other candidates for the common link between Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end-binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are ciliary proteins involved in intraflagellar transport. Finally, pathogenetic similarities between some ciliopathies and extraintestinal tumours in FAP suggest a cilia defect. Understanding extracolonic manifestations in the context of FAP as a ciliary disorder might add new therapeutic options for patients with Gardner's syndrome.
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PMID:Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder. 1957 2

Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C-terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons.
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PMID:Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2. 2727 32