dimanche 27 novembre 2011

Mutated genes in cancer (34) – FAM123B

FAM123B (also known as WTX and AMER1)

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 139285 or FAM123B
● Ensembl (http://www.ensembl.org/index.html): ENSG00000184675
● UniProt (http://www.uniprot.org/): Q5JTC6
● GeneCards (http://www.genecards.org/): FAM123B
● HGNC (http://www.genenames.org/): 26837 or FAM123B

Gene locus:


Protein name:

Family with sequence similarity 123B

Protein Size:

1135 amino acids; about 124 kDa


Fam123B forms a protein complex with β -catenin, axin1, β-transducin repeat-containing protein 2 (β-TrCP2) and APC and negatively regulates the Wnt signaling pathway by promoting the ubiquitination and degradation of β-catenin. Fam123B also plays a role in the recruitment of APC from microtubules to the plasma membrane and appears to be involved in the maintenance of intercellular junctions. Fam123B enhances trancription activation by the Wilms tumor protein (WT1).

Cancer-related alterations:

Somatic tumor-specific FAM123B mutations have been observed in kidney and colorectal cancers and in acute myeloid leukemia (AML). In Wilms tumors, the most commonly observed mutation is the deletion of the entire FAM123B gene. Truncation mutations and missense mutations have also been observed. 7-29% of Wilms tumors show deletions or mutations of FAM123B. Inactivating mutations in FAM123B (deletions and truncating/frameshift mutations) appear to be negatively correlated in Wilms tumors with activating mutations in exon 3 of CTNNB1 (encoding β-catenin), implicating the activation of the Wnt signaling pathway in the formation of Wilms tumors since both inactivating mutations of FAM123B and activating mutations of CTNNB1 function to activate this signaling pathway.

References (open access):

The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity. Rivera MN, Kim WJ, Wells J, Stone A, Burger A, Coffman EJ, Zhang J, Haber DA. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8338-43.

The WTX/AMER1 gene family: evolution, signature and function. Boutet A, Comai G, Schedl A. BMC Evol Biol. 2010 Sep 15;10:280.

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