Hsk1- and SCF(Pof3)-dependent proteolysis of S. pombe Ams2 ensures histone homeostasis and centromere function.
Hsk1- and SCF(Pof3)-dependent proteolysis of S. pombe Ams2 ensures histone homeostasis and centromere function.
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DOI：
10.1016/j.devcel.2009.12.024
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发表时间：
2010-03-16
影响因子：
11.8
通讯作者：
Saitoh, Shigeaki
中科院分区：
文献类型：
--
作者：
Takayama, Yuko;Mamnun, Yasmine M.;Trickey, Michelle;Dhut, Susheela;Masuda, Fumie;Yamano, Hiroyuki;Toda, Takashi;Saitoh, Shigeaki
粟酒裂殖酵母加塔因子Ams 2负责细胞周期依赖性的所有核心组蛋白基因的转录激活，在G1/S期达到峰值。有趣的是，它自身的蛋白质水平也同时波动。在这里，我们表明，Ams 2是泛素化和降解SCF（Skp 1-Cdc 53/Cullin-1-F-box）泛素连接酶，其中F盒蛋白Pof 3结合这种蛋白质。Ams 2在多个位点磷酸化，这是SCFPof 3依赖性蛋白水解所必需的。Hsk 1/Cdc 7激酶与Ams 2物理结合并磷酸化Ams 2。即使是轻度过表达的Ams 2诱导组成性组蛋白表达和染色体不稳定性，其毒性被夸大时，HSK 1功能受损。这部分归因于典型的H3异常掺入中央CENP-A/Cnp 1丰富的着丝粒，从而逆转特定的染色质结构，明显正常的核小体。我们认为Hsk 1在后S期通过SCFPof 3介导的Ams 2降解在基因组稳定性中起着至关重要的作用，从而维持了着丝粒的完整性。细胞周期调控组蛋白转录因子Ams 2仅在G1/S期稳定Ams 2在S期被DDK磷酸化，推测为G2期磷酸化Ams 2被SCFpof 3泛素化并通过蛋白酶体降解异位Ams 2表达干扰组蛋白稳态和着丝粒功能
Schizosaccharomyces pombe GATA factor Ams2 is responsible for cell cycle-dependent transcriptional activation of all the core histone genes peaking at G1/S phase. Intriguingly, its own protein level also fluctuates concurrently. Here, we show that Ams2 is ubiquitylated and degraded through the SCF (Skp1-Cdc53/Cullin-1-F-box) ubiquitin ligase, in which F box protein Pof3 binds this protein. Ams2 is phosphorylated at multiple sites, which is required for SCFPof3-dependent proteolysis. Hsk1/Cdc7 kinase physically associates with and phosphorylates Ams2. Even mild overexpression of Ams2 induces constitutive histone expression and chromosome instability, and its toxicity is exaggerated when Hsk1 function is compromised. This is partly attributable to abnormal incorporation of canonical H3 into the central CENP-A/Cnp1-rich centromere, thereby reversing specific chromatin structures to apparently normal nucleosomes. We propose that Hsk1 plays a vital role during post S phase in genome stability via SCFPof3-mediated degradation of Ams2, thereby maintaining centromere integrity. ► Cell cycle-regulated histone transcription factor Ams2 is stable only during G1/S ► Ams2 gets phosphorylated by DDK during S phase and presumably G2 phase ► Phosphorylated Ams2 is ubiquitylated by SCFpof3 and degraded via the proteasome ► Ectopic Ams2 expression interferes with histone homeostasis and centromere function
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影响因子：
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