Department of Dermatology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City 231, Taiwan.
School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
Mol Cells. 2018 Jun;41(6):562-574. doi: 10.14348/molcells.2018.2347. Epub 2018 Jun 14.
The tazarotene-induced gene 1 (TIG1) protein is a retinoid-inducible growth regulator and is considered a tumor suppressor. Here, we show that DnaJ heat shock protein family member C8 (DNAJC8) is a TIG1 target that regulates glycolysis. Ectopic DNAJC8 expression induced the translocation of pyruvate kinase M2 (PKM2) into the nucleus, subsequently inducing glucose transporter 1 (GLUT1) expression to promote glucose uptake. Silencing either DNAJC8 or PKM2 alleviated the upregulation of GLUT1 expression and glucose uptake induced by ectopic DNAJC8 expression. TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. In conclusion, TIG1 acts as a pivotal repressor of DNAJC8 to enhance glucose uptake by partially regulating PKM2 translocation.
TIG1 蛋白是维 A 酸诱导基因 1（TIG1）蛋白，是一种维 A 酸诱导的生长调节剂，被认为是一种肿瘤抑制因子。在这里，我们表明 DnaJ 热休克蛋白家族成员 C8（DNAJC8）是 TIG1 的靶标，可调节糖酵解。过表达 DNAJC8 可诱导丙酮酸激酶 M2（PKM2）易位入核，进而诱导葡萄糖转运蛋白 1（GLUT1）表达，促进葡萄糖摄取。沉默 DNAJC8 或 PKM2 可减轻过表达 DNAJC8 诱导的 GLUT1 表达和葡萄糖摄取的上调。TIG1 在细胞质中与 DNAJC8 相互作用，这种相互作用完全阻断了 DNAJC8 介导的 PKM2 易位并抑制了葡萄糖摄取。此外，在沉默 TIG1 的细胞中观察到葡萄糖摄取增加。总之，TIG1 作为 DNAJC8 的关键抑制剂，通过部分调节 PKM2 易位来增强葡萄糖摄取。
