Disease relevance of CENTD3

• Our results demonstrate the usefulness of antisense EST libraries for global chromosomal gene inactivation, establish the practicality of loss-of-function phenotypic screens for the identification of genomic loci required for pathogen effects in mammalian cells, and reveal an important role for ARAP3 in cellular internalization of anthrax toxin [1].

Psychiatry related information on CENTD3

• Moving beyond the contest framework of early king shows, new drag king troupes like Minneapolis' Dykes Do Drag are "mixing it up" in an attempt to complicate notions of butch/femme gender roles, sexuality, and drag stereotypes [2].
• Drawing on interview material the chapter suggests that just as Drag Kings and kinging has been a useful and provocative site for closer and deeper understandings of genders, bodies and sexualities, Drag Kings and Kinging may also provide a useful site for unraveling some of the minefield that is race and racism [3].

High impact information on CENTD3

• Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices [4].
• EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin [1].
• This phenotypic screen and subsequent analysis identified ARAP3, which is a phosphoinositide-binding protein implicated previously in membrane vesicle trafficking and cytoskeletal organization, as a mammalian host-cell gene that is essential for normal anthrax toxicity [1].
• Our results indicate that ARAP3 is a Rap-effector that plays an important role in mediating PI3K-dependent crosstalk between Ras, Rho, and Arf family small GTPases [5].
• We report here that as a Rho GAP, ARAP3 prefers RhoA as a substrate and that it can be activated in vitro by the direct binding of Rap proteins to a neighbouring Ras binding domain (RBD) [5].

Biological context of CENTD3

• In contrast, ARAP3 dramatically slowed the kinetics of cell spreading on fibronectin but had no effect on cell adhesion [6].
• Mutation of two phosphorylation sites, Y1399 and Y1404, enhanced some ARAP3 activities, suggesting that ARAP3 may be negatively regulated by phosphorylation on these tyrosine residues [6].

Anatomical context of CENTD3

• Inducible expression of ARAP3 in HEK293 epithelial cells resulted in increased cell rounding, membrane process formation and cell clustering on ECM substrates [6].
• We found no evidence for direct regulation of ARAP3's Rho GAP activity by PtdIns(3,4,5)P(3) in vitro, but PI3K activity was required for activation by Rap in a cellular context, suggesting that PtdIns(3,4,5)P(3)-dependent translocation of ARAP3 to the plasma membrane may be required for further activation by Rap [5].
• ARAP3 is essential for formation of lamellipodia after growth factor stimulation [7].
• To investigate the physiological function of ARAP3, we used an RNAi-based approach in an endothelial cell model [7].

Associations of CENTD3 with chemical compounds

• We have identified ARAP3 as a phosphorylated target of protein tyrosine kinases [6].

References