High impact information on ASC1

• We also show that purified Asc1p-deficient ribosomes have increased translational activity compared to that of wild-type yeast ribosomes [1].
• Further, we demonstrate that asc1Delta null strains have increased levels of specific proteins in vivo and that this molecular phenotype is complemented by either Asc1p or RACK1 [1].
• Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression [1].
• Mutations that activate Gcn4p function, such as gcd7-201, cpc2, and deletion of the translational regulatory region of the GCN4 gene, also cause salt sensitivity [2].
• RACK1 recruits activated protein kinase C to the ribosome, which leads to the stimulation of translation through the phosphorylation of initiation factor 6 and, potentially, of mRNA-associated proteins [3].

Biological context of ASC1

• RACK1 therefore links signal-transduction pathways directly to the ribosome, which allows translation to be regulated in response to cell stimuli [3].

Anatomical context of ASC1

• In addition, the fact that RACK1 associates with membrane-bound receptors indicates that it promotes the docking of ribosomes at sites where local translation is required, such as focal adhesions [3].
• Asc1p, a WD40-domain containing adaptor protein, is required for the interaction of the RNA-binding protein Scp160p with polysomes [4].

Associations of ASC1 with chemical compounds

• Here, we show that CPC2 transcription depends on the carbon source and is induced during utilization of the sugar glucose [5].
• Increased amounts of the Fhl1p co-regulator Ifh1p induce CPC2 transcription even when ethanol is utilized [5].
• Whereas Gpa2 promotes glucose signaling through elevated production of cAMP, Asc1 has opposing effects on these same processes [6].

Regulatory relationships of ASC1

• Cpc2p seems to be part of an additional control of Gcn4p activity, independent of its translational regulation [7].
• Loss of CPC2 gene function suppresses a deletion of the GCN2 gene encoding the general control sensor kinase, but not a deletion in the GCN4 gene [7].
• Deletion of CPC2/ASC1 abolished amino acid starvation-induced adhesive growth and impaired basal expression of FLO11 and its activation upon starvation in haploid cells [8].

Other interactions of ASC1

• The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino-acid starvation [7].
• Deletion of FHL1 reduces CPC2 transcription significantly in presence of glucose, but has no effect when the non-fermentable carbon source ethanol is provided [5].
• We propose that the absence of functional Asc1p allows the growth of hap1-hem1- cells by reducing the efficiency of translation [9].
• Two of these associated proteins, Mpt4p and Asc1p, were nearly stoichiometrically bound to the ribosome [10].
• The interaction of Scp160p with ribosomes depends on Asc1p [4].

Analytical, diagnostic and therapeutic context of ASC1

• Interestingly, RACK1 is also a constituent of the eukaryotic ribosome, and a recent cryo-electron microscopy study localized it to the head region of the 40S subunit in the vicinity of the messenger RNA (mRNA) exit channel [3].

References