Hsk1- and SCF^Pof3-Dependent Proteolysis of S. pombe Ams2 Ensures Histone Homeostasis and Centromere Function

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• 作者：Yuko Takayama ; Yasmine M. Mamnun ; Michelle Trickey ; Susheela Dhut ; Fumie Masuda ; Hiroyuki Yamano ; Takashi Toda ; Shigeaki Saitoh
• 刊名：Developmental Cell
• 出版年：2010
• 出版时间：16 March 2010
• 年：2010
• 卷：18
• 期：3
• 页码：385-396
• 全文大小：1420 K

文摘

Summary

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 SCF^Pof3-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 SCF^Pof3-mediated degradation of Ams2, thereby maintaining centromere integrity.