Disease relevance of Hsc70-3

• Our studies in the NG108-15 neuroblastoma x glioma cell line previously showed that the molecular chaperonin, Hsc70, is an ethanol-responsive gene (EtRG) regulated at the level of transcription by ethanol [1].

High impact information on Hsc70-3

• Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in Drosophila, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines [2].
• Hsc70 is required for endocytosis and clathrin function in Drosophila [3].
• Consistent with these phenotypes, recombinant mutant Hsc70 proteins exhibited diminished clathrin uncoating activity in vitro [3].
• We demonstrate that the functions of both Hsc3p and Hsc4p are required for proper tissue establishment and maintenance [4].
• We believe that the amino acid substitutions in Hsc3p interfere with the structural coupling of ATP binding to substrate release, and this defect is the basis for the mutant proteins' dominant negative effects in vivo [4].

Biological context of Hsc70-3

• DNA sequence analysis predicts that HSC3 encodes a 72-kDa protein with a hydrophobic leader sequence and a C-terminal retrieval tetrapeptide, KDEL, characteristics associated with luminal endoplasmic reticulum (ER) proteins [5].
• Stable transfection studies show that GRP78 transcription is also regulated by ethanol and that ethanol also potentiates GRP78 induction by classical inducing agents such as tunicamycin [1].

Anatomical context of Hsc70-3

• A comparison of the deduced aa sequences of these and hsc70 proteins from different species indicates that hsc70 proteins residing in the same intracellular compartment in different organisms are more similar to each other than are hsc70s from the same organism, but different organelles [5].

Associations of Hsc70-3 with chemical compounds

• We recently identified two related molecular chaperonins, GRP94 and GRP78, as EtRGs with GRP94 mRNA abundance being induced by ethanol more than three-fold vs. control [1].
• GRP94 and GRP78 (GRP94/78) are known to be induced by agents which inhibit glycoprotein processing or deplete endoplasmic reticulum stores of calcium [1].

Analytical, diagnostic and therapeutic context of Hsc70-3

• Genomic structure and sequence analysis of Drosophila melanogaster HSC70 genes [5].

References