Selective autophagy of the endoplasmic reticulum, namely ER-phagy, is mediated by ER-localized receptors, which are recognized and sequestered by GABARAP/LC3B-decorated phagophores, and transferred to lysosomes for degradation. Being one such receptor, FAM134B plays critical roles in cellular processes such as protein quality control and neuronal survival. FAM134B has also been associated with different cancers, although its exact role remains elusive. We report here that the FAM134B gene encodes not one but at least two different protein isoforms; the full length, and the N-terminally truncated forms. Their relative expression shows extreme variation, both within normal tissues and among cancer types. Expression of full length FAM134B is restricted to the brain, testis, spleen and prostate. In contrast, N-terminally truncated FAM134B is dominant in the heart, skeletal muscle, kidney, pancreas and liver. We compared wild-type and knockout mice to study the role of the Fam134b gene in starvation. N-terminally truncated FAM134B-2 was induced in the liver, skeletal muscle and heart, but not in the pancreas and stomach following starvation. Upon starvation, Fam134b^-/- mice differed from wild-type mice by less weight loss, less hyperaminoacidemic and hypocalcemic response, but increased levels of serum albumin, total serum proteins and α-amylase. Interestingly, either N-terminally truncated FAM134B or both isoforms were down-regulated in liver, lung and colon cancers. In contrast, upregulation was observed in stomach and chromophobe kidney cancers.

中文翻译：

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全长和 N 端截短的 FAM134B 亚型在正常生理和癌症中的差异表达

内质网的选择性自噬，即内质网自噬，由内质网定位受体介导，由 GABARAP/LC3B 修饰的吞噬细胞识别和隔离，并转移到溶酶体进行降解。作为一种这样的受体，FAM134B 在蛋白质质量控​​制和神经元存活等细胞过程中发挥着关键作用。FAM134B 也与不同的癌症有关，尽管它的确切作用仍然难以捉摸。我们在此报告 FAM134B 基因编码的不是一种而是至少两种不同的蛋白质亚型；全长和 N 端截断的形式。它们的相对表达在正常组织和癌症类型之间显示出极大的变化。全长 FAM134B 的表达仅限于脑、睾丸、脾脏和前列腺。相比之下，N-末端截短的 FAM134B 在心脏、骨骼肌、肾脏、胰腺和肝脏中占主导地位。我们比较了野生型和基因敲除小鼠，以研究 Fam134b 基因在饥饿中的作用。N-末端截短的 FAM134B-2 在肝脏、骨骼肌和心脏中被诱导，但在饥饿后不在胰腺和胃中被诱导。饥饿时，Fam134b^-/-小鼠与野生型小鼠的不同之处在于体重减轻较少、高氨基酸血症和低血钙反应较少，但血清白蛋白、总血清蛋白和 α-淀粉酶水平升高。有趣的是，在肝癌、肺癌和结肠癌中，N 末端截短的 FAM134B 或两种同工型都被下调。相反，在胃癌和嫌色肾癌中观察到上调。