UBLCP1 是一种 26S 蛋白酶体磷酸酶，可调节核蛋白酶体活性。
UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity.
机构信息
Department of Pharmacology, University of California-San Diego, La Jolla, CA 92093-0721, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18649-54. doi: 10.1073/pnas.1113170108. Epub 2011 Sep 26.
Abstract
Protein degradation by the 26S proteasome is a fundamental process involved in a broad range of cellular activities, yet how proteasome activity is regulated remains poorly understood. We report here that ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) is a 26S proteasome phosphatase that regulates nuclear proteasome activity. UBLCP1 directly interacts with the proteasome via its UBL domain and is exclusively localized in the nucleus. UBLCP1 dephosphorylates the 26S proteasome and inhibits proteasome activity in vitro. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. Our results describe the first identified proteasome-specific phosphatase and uncover a unique mechanism for phosphoregulation of the proteasome.
摘要
26S 蛋白酶体的蛋白质降解是参与广泛细胞活动的基本过程，但蛋白酶体活性如何调节仍知之甚少。我们在这里报告说，泛素样结构域包含 C 端结构域磷酸酶 1（UBLCP1）是一种 26S 蛋白酶体磷酸酶，可调节核蛋白酶体活性。UBLCP1 通过其 UBL 结构域直接与蛋白酶体相互作用，并且仅在核内定位。UBLCP1 去磷酸化 26S 蛋白酶体并在体外抑制蛋白酶体活性。细胞中 UBLCP1 的敲低促进 26S 蛋白酶体组装，并选择性增强核蛋白酶体活性。我们的结果描述了第一个鉴定的蛋白酶体特异性磷酸酶，并揭示了蛋白酶体磷酸化调节的独特机制。
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1
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Mol Cell. 2011 Jun 10;42(5):637-49. doi: 10.1016/j.molcel.2011.04.021.
2
Selective inactivation of a human neuronal silencing phosphatase by a small molecule inhibitor.小分子抑制剂选择性失活人神经元沉默磷酸酶。
ACS Chem Biol. 2011 May 20;6(5):511-9. doi: 10.1021/cb100357t. Epub 2011 Feb 24.
3
Calcineurin B subunit interacts with proteasome subunit alpha type 7 and represses hypoxia-inducible factor-1α activity via the proteasome pathway.钙调神经磷酸酶 B 亚基与蛋白酶体亚基 α 型 7 相互作用，并通过蛋白酶体途径抑制低氧诱导因子-1α 活性。
Biochem Biophys Res Commun. 2011 Feb 18;405(3):468-72. doi: 10.1016/j.bbrc.2011.01.055. Epub 2011 Jan 20.
4
Deconstruction for reconstruction: the role of proteolysis in neural plasticity and disease.去结构重建：蛋白水解在神经可塑性和疾病中的作用。
Neuron. 2011 Jan 13;69(1):22-32. doi: 10.1016/j.neuron.2010.11.006.
5
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6
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7
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8
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9
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Mol Cell. 2010 Jun 11;38(5):627-35. doi: 10.1016/j.molcel.2010.05.003.
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