Lennon K, Bird A, Kukuruzinska M A
Division of Oral Biology, Boston University School of Dental Medicine, Massachusetts, USA.
Biochem Biophys Res Commun. 1997 Aug 28;237(3):562-5. doi: 10.1006/bbrc.1997.7190.
The evolutionarily conserved ALG7 gene encodes the dolichol-P-dependent N-acetylglucosamine-1-P transferase (GPT) and functions by initiating the dolichol pathway of protein N-glycosylation. In Saccharomyces cerevisiae, ALG7 has been shown to play a role in cell proliferation. The yeast alpha-factor-induced cell cycle arrest in G1 occurs, in part, by downregulation of CLN1 and CLN2. The function of ALG7 in G1 arrest was examined in alg7 mutants containing diminished GPT activity. In wild type, CLN1 and CLN2 mRNAs were rapidly downregulated, while in alg7 mutants, these transcripts were only transiently repressed before becoming greatly augmented. Analyses of DNA contents and budding indices showed that alg7 mutants resumed cycling when wild type cells remained arrested. Thus, deregulation of ALG7 interferes with cell cycle arrest by preventing a sustained downregulation of CLN1 and CLN2 mRNAs. These results provide a molecular insight into the role of ALG7, and protein N-glycosylation in general, in proliferation.
进化上保守的ALG7基因编码依赖于多萜醇磷酸的N-乙酰葡糖胺-1-磷酸转移酶(GPT),并通过启动蛋白质N-糖基化的多萜醇途径发挥作用。在酿酒酵母中,ALG7已被证明在细胞增殖中起作用。酵母α因子诱导的G1期细胞周期停滞部分是通过CLN1和CLN2的下调发生的。在GPT活性降低的alg7突变体中研究了ALG7在G1期停滞中的功能。在野生型中,CLN1和CLN2 mRNA迅速下调,而在alg7突变体中,这些转录本在大幅增加之前仅被短暂抑制。DNA含量和出芽指数分析表明,当野生型细胞保持停滞时,alg7突变体恢复了细胞周期运转。因此,ALG7的失调通过阻止CLN1和CLN2 mRNA的持续下调而干扰细胞周期停滞。这些结果为ALG7以及一般蛋白质N-糖基化在增殖中的作用提供了分子层面的见解。