NF-κB induction of the SUMO protease SENP2: A negative feedback loop to attenuate cell survival response to genotoxic stress.
NF-κB induction of the SUMO protease SENP2: A negative feedback loop to attenuate cell survival response to genotoxic stress.
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DOI：
10.1016/j.molcel.2011.06.017
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发表时间：
2011-07-22
期刊：
影响因子：
16
通讯作者：
Miyamoto S
中科院分区：
文献类型：
--
作者：
Lee MH;Mabb AM;Gill GB;Yeh ET;Miyamoto S
Activation of NF-κB, pivotal for immunity and oncogenesis, is tightly controlled by multiple feedback mechanisms. In response to DNA damage, SUMOylation of NEMO (NF-κB essential modulator) is critical for NF-κB activation, however SUMO proteases and feedback mechanisms involved remain unknown. Here we show that among the six known SENPs (Sentrin/SUMO-specific proteases) only SENP2 can efficiently associate with NEMO, deSUMOylate NEMO and inhibit NF-κB activation induced by DNA damage. We further show that NF-κB induces SENP2 (and SENP1) transcription selectively in response to genotoxic stimuli, which involves ATM (ataxia telangiectasia mutated)-dependent histone methylation of SENP2 promoter κB regions and NF-κB recruitment. SENP2-null cells display biphasic NEMO SUMOylation and activation of IKK and NF-κB, and higher resistance to DNA damage-induced cell death. Our study establishes a self-attenuating feedback mechanism selective to DNA damage induced signaling to limit NF-κB-dependent cell survival responses.
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