在过氧化氢诱导的酿酒酵母凋亡过程中，无菌20激酶使组蛋白H2B的丝氨酸10位点发生磷酸化。

Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae.

作者信息

Ahn Sung-Hee, Cheung Wang L, Hsu Jer-Yuan, Diaz Robert L, Smith M Mitchell, Allis C David

机构信息

Laboratory of Chromatin Biology, The Rockefeller University, Box 78, New York, NY 10021, USA.

出版信息

Cell. 2005 Jan 14;120(1):25-36. doi: 10.1016/j.cell.2004.11.016.

DOI:10.1016/j.cell.2004.11.016

PMID:15652479

Abstract

Apoptosis is a highly coordinated cell suicide mechanism in vertebrates. Phosphorylation of serine 14 of histone H2B, catalyzed by Mst1 kinase, has been linked to chromatin compaction during apoptosis. We extend these results to unicellular eukaryotes by demonstrating that H2B is specifically phosphorylated at serine 10 (S10) in a hydrogen peroxide-induced cell death pathway in S. cerevisiae. H2B S10A mutants are resistant to cell death elicited by H(2)O(2) while H2B S10E phospho-site mimics promote cell death and induce the "constitutive" formation of condensed chromatin. Ste20 kinase, a yeast homolog of mammalian Mst1 kinase, translocates into the nucleus in a caspase-independent fashion and directly phosphorylates H2B at S10. Conservation of targeted H2B phosphorylation and the enzyme system responsible for the process point to an ancient mechanism of chromatin remodeling that likely plays an important role in governing cellular homeostasis in a wide range of organisms.

摘要

细胞凋亡是脊椎动物中一种高度协调的细胞自杀机制。由Mst1激酶催化的组蛋白H2B丝氨酸14的磷酸化，与细胞凋亡过程中的染色质压缩有关。我们通过证明在酿酒酵母中过氧化氢诱导的细胞死亡途径中H2B在丝氨酸10（S10）处被特异性磷酸化，将这些结果扩展到单细胞真核生物。H2B S10A突变体对H₂O₂引发的细胞死亡具有抗性，而H2B S10E磷酸化位点模拟物则促进细胞死亡并诱导凝聚染色质的“组成型”形成。Ste20激酶是哺乳动物Mst1激酶的酵母同源物，以不依赖于半胱天冬酶的方式转运到细胞核中，并直接在S10处磷酸化H2B。靶向H2B磷酸化和负责该过程的酶系统的保守性表明存在一种古老的染色质重塑机制，该机制可能在控制广泛生物体中的细胞内稳态方面发挥重要作用。