Anti-COPB1 monoclonal antibody, clone N4B6

Combining glycolytic inhibition, with other anti-cancer therapies is a potential approach to treating cancer. In this context, we attempted to identify genes that determine sensitivity to 2-deoxyglucose (2DG), a glycolytic inhibitor, in cancer cells using pooled shRNA libraries targeting 15,000 genes. The screen revealed that COPB1 and ARCN1, which are essential in retrograde transport, as determinants of sensitivity to 2DG: silencing of COPB1 or ARCN1 expression sensitized cells to 2DG toxicity. To address the mechanism of potentiation of 2DG toxicity by inhibition of COPI-mediated transport, we focused on the role of lipolysis as an alternate source of energy upon inhibition of glycolysis. In the process of lipolysis, COPI-mediated transport is required for localization to lipid droplets of adipose triglyceride lipase (ATGL), a key enzyme that produces fatty acids from triacylglycerol as a substrate for beta-oxidation. The ATGL inhibitor atglistatin potentiated 2DG toxicity, consistent with a model in which a defect in COPI-mediated transport of ATGL to lipid droplets inhibits energy supply, thereby sensitizing cells to glycolytic inhibition. Collectively, our data demonstrated that a defect in COPI-mediated transport or pharmacological inhibition of ATGL potentiates 2DG toxicity in cancer cells, possibly due to a reduction in the energy supply. (C) 2015 Elsevier Inc. All rights reserved.

Porcine MYOD1 gene has been mapped to swine chromosome (SSC) 2p14-p17, which is involved in the regulation of the proliferation and differentiation of skeletal muscle cells. The LDHA (lactate dehydrogenase A) and COPB1 (coatomer protein complex, subunit beta 1) genes, which map close to MYOD1, are involved in energy metabolism and protein transport processes. Both genes might play important roles in muscle development. However, little is known about the porcine LDHA and COPB1 genes. In the present study, the full-length cDNA of these two genes were cloned. The mapping results demonstrated that porcine LDHA and COPB1 were all mapped to SSC 2p14-p17. In this region, there are several QTL for growth and carcass traits, including average backfat thickness, lean and fat percentage. The RT-PCR results revealed that both LDHA and COPB1 were highly expressed in porcine skeletal muscle tissues, implying their potential regulatory function of muscle development. LDHA and COPB1 were then mapped to the region and multipoint analyses generated a best sex-averaged map order of each gene between linked markers: MYOD1_75.2 cM _LDHA_79 cM _CSRP3_83.8 cM _TEF-1_86.5 cM _COPB1_90 cM. Association analyses revealed that the substitution of c.423A > G had a significant effect on average daily gain on test, average backfat thickness (BFT), loin muscle area, lumbar BFT, marbling score, tenth rib BFT, average drip loss and fiber type II ratio. The substitution of c.3096C > T had a significant effect on average BFT, lumbar BFT, tenth rib BFT, carcass weight and last rib BFT. Interestingly, both SNPs were all associated with average BFT, lumbar BFT and tenth rib BFT.