Activation of a Novel Ubiquitin-Independent Proteasome Pathway when RNA Polymerase II Encounters a Protein Roadblock
Activation of a Novel Ubiquitin-Independent Proteasome Pathway when RNA Polymerase II Encounters a Protein Roadblock
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DOI：
10.1128/mcb.00403-13
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发表时间：
2013-10-01
影响因子：
5.3
通讯作者：
Liu, Leroy F.
中科院分区：
文献类型：
--
作者：
Ban, Yi;Ho, Chia-Wen;Liu, Leroy F.
已知拓扑异构酶 II beta (Top2 beta)-DNA 裂解复合物可阻止 RNA 聚合酶 II (RNAPII) 的延伸，引发 RNAPII 大亚基 (RNAPII LS) 和 Top2 beta 本身的蛋白酶体降解，作为 DNA 修复的前奏。在这里，我们证明 Top2 beta 的降解是通过一种新颖的不依赖于泛素的机制发生的，该机制仅需要 19S AAA ATP 酶和 20S 蛋白酶体。我们的结果表明，当 RNAPII 因 Top2 蛋白路障而持续停滞时，19S AAA ATP 酶在感知 Top2 β 裂解复合物和协调 20S 蛋白酶体对其降解方面发挥双重作用。阐明这种转录相关的蛋白酶体途径可以阐明 19S AAA ATP 酶在转录延伸过程中处理紧密的蛋白质-DNA 复合物中的一般作用。
Topoisomerase II beta (Top2 beta)-DNA cleavage complexes are known to arrest elongating RNA polymerase II (RNAPII), triggering a proteasomal degradation of the RNAPII large subunit (RNAPII LS) and Top2 beta itself as a prelude to DNA repair. Here, we demonstrate that the degradation of Top2 beta occurs through a novel ubiquitin-independent mechanism that requires only 19S AAA ATPases and 20S proteasome. Our results suggest that 19S AAA ATPases play a dual role in sensing the Top2 beta cleavage complex and coordinating its degradation by 20S proteasome when RNAPII is persistently stalled by the Top2 protein roadblock. Clarification of this transcription-associated proteasome pathway could shed light on a general role of 19S AAA ATPases in processing tight protein-DNA complexes during transcription elongation.