bHLH proteins involved in Drosophila neurogenesis are mutually regulated at the level of stability.
bHLH proteins involved in Drosophila neurogenesis are mutually regulated at the level of stability.
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DOI：
10.1093/nar/gkv083
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发表时间：
2015-03-11
影响因子：
14.9
通讯作者：
Delidakis C
中科院分区：
文献类型：
--
作者：
Kiparaki M;Zarifi I;Delidakis C
前神经bHLH激活剂在所有神经外胚层区域表达，预示着中枢和外周神经发生的事件。果蝇Sc是一种典型的前神经激活剂，其与E-蛋白Daughterless（Da）异二聚化，并且被E（spl）阻遏物等拮抗。我们确定了调节果蝇S2细胞中Sc稳定性的参数。我们发现，Sc是一个非常不稳定的磷蛋白，其营业额发生通过至少三个蛋白酶体依赖的机制。(i)当Sc超过Da时，其降解通过其反式激活结构域（transactivation domain，简写为Sc）促进。(ii)在DNA结合的Da/Sc异源二聚体中，Sc降解通过SPTSS磷酸化基序促进，并且Da的AD 1酶在该过程中得以保留。(iii)当E（spl）m7表达时，它与Sc或Da/Sc复合，并以需要辅阻遏物Groucho和Sc SPTSS基序的方式促进它们的降解。Da/Sc_2促进E（spl）m7降解。由于E（spl）m7是Notch的直接靶标，因此Sc和E（spl）的相互不稳定可能部分有助于Notch的高度保守的抗神经活性。缺乏SPTSS基序的Sc变体在转基因果蝇中显着稳定并过度活跃。我们的研究结果提出了一种新的神经发生调控机制，涉及到该过程中关键参与者的稳定性。
Proneural bHLH activators are expressed in all neuroectodermal regions prefiguring events of central and peripheral neurogenesis. Drosophila Sc is a prototypical proneural activator that heterodimerizes with the E-protein Daughterless (Da) and is antagonized by, among others, the E(spl) repressors. We determined parameters that regulate Sc stability in Drosophila S2 cells. We found that Sc is a very labile phosphoprotein and its turnover takes place via at least three proteasome-dependent mechanisms. (i) When Sc is in excess of Da, its degradation is promoted via its transactivation domain (TAD). (ii) In a DNA-bound Da/Sc heterodimer, Sc degradation is promoted via an SPTSS phosphorylation motif and the AD1 TAD of Da; Da is spared in the process. (iii) When E(spl)m7 is expressed, it complexes with Sc or Da/Sc and promotes their degradation in a manner that requires the corepressor Groucho and the Sc SPTSS motif. Da/Sc reciprocally promotes E(spl)m7 degradation. Since E(spl)m7 is a direct target of Notch, the mutual destabilization of Sc and E(spl) may contribute in part to the highly conserved anti-neural activity of Notch. Sc variants lacking the SPTSS motif are dramatically stabilized and are hyperactive in transgenic flies. Our results propose a novel mechanism of regulation of neurogenesis, involving the stability of key players in the process.
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影响因子：
64.5
作者：
CAUDY, M;VASSIN, H;JAN, YN
通讯作者：
JAN, YN
影响因子：
10.5
作者：
Aragon, Eric;Goerner, Nina;Macias, Maria J.
通讯作者：
Macias, Maria J.
影响因子：
10.5
作者：
BAILEY, AM;POSAKONY, JW
通讯作者：
POSAKONY, JW
DOI：
10.1073/pnas.89.18.8731
发表时间：
1992-09-15
影响因子：
11.1
作者：
DELIDAKIS, C;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
影响因子：
10.5
作者：
Culí, J;Modolell, J
通讯作者：
Modolell, J