Disease relevance of Wdr1

• Structural organization and developmental expression pattern of the mouse WD-repeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus [1].
• We report the isolation and characterisation of the gene WDR9 (WD Repeat 9), located in the Down Syndrome critical region-2 (DCR-2) from the human chromosome 21 [2].

High impact information on Wdr1

• We have identified a WD repeat host protein that was recruited to and actively retained on phagosomes by living, but not dead, mycobacteria [3].
• In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes [4].
• The WD repeat scaffolding protein RACK1 can mediate integration of the insulin-like growth factor I receptor (IGF-IR) and integrin signaling in transformed cells [5].
• One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12 [6].
• Coronins are a conserved family of WD repeat-containing, actin-binding proteins that regulate cell motility in a variety of model organisms [7].

Biological context of Wdr1

• This could lead to permanent overexpresssion of the ect-2, calnexin, and Wdr1 genes and suppression of expression of the DRIP/TRAP-80 gene that we observed, which likely contribute to induction and maintenance of transformed phenotypes [8].
• Expression of the calnexin gene (encoding a type I membrane protein/molecular chaperone), the ect-2 proto-oncogene, and the stress-inducible gene, Wdr1, was upregulated [9].
• Deletion of the C-terminal 41 residues of HEED, spanning the seventh WD repeat, as in the 494-residue HEED protein, was detrimental to HEED-MA interaction in vivo, suggesting the existence of another C-terminal binding site and/or a conformational role of the HEED C-terminal domain in the MA-HEED interaction [10].
• To the best of our knowledge, this is the first report of tyrosine phosphorylation of a member of the WD repeat family of proteins [11].
• Alix/AIP1 is a cytoplasmic protein, which was first characterized as an interactor of ALG-2, a calcium-binding protein necessary for cell death [12].

Anatomical context of Wdr1

• In contrast, neither the coiled coil nor the positively charged residues within the linker domain were required for plasma membrane binding, suggesting that the N-terminal, WD repeat-containing domain mediates membrane interaction [13].
• Association with the cytoskeleton was mediated by trimerization of a stretch of positively charged residues within a linker region between the N-terminal, WD repeat-containing domain and the C-terminal coiled coil [13].
• The WD-repeat protein family consists of a large group of structurally related yet functionally diverse proteins found predominantly in eukaryotic cells [14].
• Isolation and characterization of human and mouse WDR19,a novel WD-repeat protein exhibiting androgen-regulated expression in prostate epithelium [15].

Associations of Wdr1 with chemical compounds

• The polysaccharide fraction AIP1 from Artemisia iwayomogi suppresses apoptotic death of the mouse spleen cells in culture [16].
• Apoptotic death of mouse thymocytes in vitro, as induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), involves the up-regulation of Fas gene expression, while a carbohydrate fraction, AIP1, from Artemisia iwayomogi suppresses the death of thymocytes in culture along with the down-regulation of Fas gene expression [17].

Other interactions of Wdr1

• Fragment R3-2 was a sequence in the mouse calnexin gene, fragment R3-1 a portion of the Wdr1 gene, and fragment R2-4 a portion of the ect-2 protooncogene [8].
• Wdr12, a mouse gene encoding a novel WD-Repeat Protein with a notchless-like amino-terminal domain [14].
• BACKGROUND: The retinoblastoma (Rb) suppressor-associated protein 46 (RbAp46) is a member of the WD-repeat protein family and a component of histone modifying and remodeling complexes [18].

References