Disease relevance of Cynisin

• Using recombinant baculovirus we expressed centaurin alpha2 and p42IP4 in Sf9 cells and purified the proteins to homogeneity [1].

High impact information on Cynisin

• The cytohesin and centaurin protein families are potential targets for PtdIns(3,4,5)P(3) that also regulate and interact with Arf GTPases [2].
• These studies identify the ADP-ribosylation factor GTPase-activating protein Centaurin alpha1 and a Tudor domain-containing hypothetical protein as putative AP-1 regulatory oncogenes [3].
• An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphatidylinositol 4,5-bisphosphate [4].
• Both negative and positive regulators of Arf, the centaurin beta family of Arf GTPase-activating proteins (GAPs) and Arf guanine nucleotide exchange factors, contain pleckstrin homology (PH) domains and are activated by phosphoinositides [5].
• In Saccharomyces cerevisiae, the protein with the highest homology to centaurin alpha is Gcs1p, the product of the GCS1 gene [6].

Biological context of Cynisin

• Recent cloning of a rat brain phosphatidylinositol 3,4, 5-trisphosphate binding protein, centaurin alpha, identified a novel gene family based on homology to an amino-terminal zinc-binding domain [6].
• Here, elucidating the gene structure for both proteins, we found the human gene for centaurin alpha2 located on chromosome 17, position 17q11.2, near to the NF1 locus, and human p42IP4 on chromosome 7, position 7p22 [1].
• Short-term down-regulation of the brain-specific, PtdIns(3,4,5)P3/Ins(1,3,4,5)P4-binding, adapter protein, p42IP4/centaurin-alpha 1 in rat brain after acoustic and electric stimulation [7].
• Centaurin beta4 proteins associate with a variety of cellular signalling components implicated in control of growth, survival and movement and may act to direct assembly and/or disassembly of molecular complexes in concert with Arf, lipid and protein phosphorylation signalling pathways [8].
• Centaurin beta4 proteins are products of the DDEF1 (development and differentiation-enhancing factor 1) locus on human chromosome 8q24.1-24 [8].

Anatomical context of Cynisin

• In contrast to p42IP4, which was distributed throughout the cell, centaurin alpha2 was concentrated at the plasma membrane already in unstimulated cells [1].

Associations of Cynisin with other chemical compounds

• Here, we have shown that similar to centaurin alpha, recombinant Gcs1p bound phosphoinositide-based affinity resins with high affinity and specificity [6].
• Using an enzyme-linked immunosorbent assay as well as confocal imaging of cells, we found that expression of centaurin alpha(1) strongly inhibited the isoproterenol-induced internalization of beta(2)-adrenoceptor [9].

Gene context of Cynisin

• From among the transcripts that were commonly up-regulated in these tumors we identified a novel human gene at chromosomal band 1p36.13, termed DDEFL1 (development and differentiation enhancing factor-like 1), encoding a product that shared structural features with centaurin-family proteins [10].
• Furthermore, fusion proteins of centaurin alpha2 and p42IP4, respectively, with the green fluorescent protein (GFP) were expressed in HEK 293 cells to visualize subcellular distribution [1].
• The protein centaurin alpha2 was released from the membrane upon addition of wortmannin, which inhibits PI3-kinase. p42IP4, however, translocated to plasma membrane upon growth factor stimulation [1].
• Two families of ARF regulatory molecules, the cytohesin ARF-Guanine nucleotide Exchange Factors and the centaurin GTPase-Activating Proteins provide key targets for the action of these lipids signals [11].

Analytical, diagnostic and therapeutic context of Cynisin

• When we carried out RT-PCR using mRNA from brain of rats of different ages we obtained several clones corresponding to p42IP4, but not to centaurin-alpha [12].

References