von Hippel–Lindau protein (pVHL) is the tumor suppressor responsible for ubiquitylating the hypoxia‐inducible factor (HIF) family of transcription factors for degradation under normoxic conditions. There are two major pVHL isoforms with the shorter isoform (pVHL₁₉) lacking the acidic domain present in the N‐terminus of the longer isoform (pVHL₃₀). Although both isoforms can degrade HIF and suppress tumor formation in experimental systems, previous research suggests that pVHL₃₀ can undergo posttranslational modifications (PTM) and interact with unique proteins. Indeed, pVHL₃₀ has long been observed to migrate as two species on a reducing polyacrylamide gel, indicating the presence of an uncharacterized PTM on the slower‐migrating pVHL₃₀ without an identifiable biological consequence. Thus, there has been considerable effort to elucidate the exclusive biological activity of pVHL₃₀, if any, by first defining the unique features of the slower‐migrating species. We show here that the migration of pVHL₃₀, but not pVHL₁₉, is retarded by 4‐(2‐aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF), an irreversible serine protease inhibitor commonly found in protease inhibitor cocktails.

中文翻译：

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pVHL 的长形式被丝氨酸蛋白酶抑制剂 AEBSF 人为修饰。

von Hippel-Lindau 蛋白 (pVHL) 是肿瘤抑制因子，负责泛素化缺氧诱导因子 (HIF) 转录因子家族，以便在常氧条件下降解。有两种主要的 pVHL 同种型，较短的同种型 (pVHL ₁₉ ) 在较长的同种型 (pVHL ₃₀ )的 N 端缺乏酸性结构域。尽管两种亚型都可以在实验系统中降解 HIF 并抑制肿瘤形成，但之前的研究表明 pVHL ₃₀可以进行翻译后修饰 (PTM) 并与独特的蛋白质相互作用。事实上，长期以来一直观察到pVHL ₃₀在还原性聚丙烯酰胺凝胶上作为两种物质迁移，这表明迁移速度较慢的 pVHL 上存在未表征的 PTM₃₀没有可识别的生物学后果。因此，通过首先定义较慢迁移物种的独特特征，已经付出了相当大的努力来阐明 pVHL ₃₀的独有生物活性（如果有的话）。我们在这里表明 pVHL ₃₀的迁移，而不是 pVHL ₁₉的迁移受到 4-（2-氨基乙基）苯磺酰氟盐酸盐（AEBSF）的阻碍，AEBSF 是一种常见于蛋白酶抑制剂混合物中的不可逆丝氨酸蛋白酶抑制剂。