PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ.
PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ.
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DOI：
10.1073/pnas.1722299115
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发表时间：
2018-07-10
影响因子：
11.1
通讯作者：
Coux O
中科院分区：
文献类型：
--
作者：
Jonik-Nowak B;Menneteau T;Fesquet D;Baldin V;Bonne-Andrea C;Méchali F;Fabre B;Boisguerin P;de Rossi S;Henriquet C;Pugnière M;Ducoux-Petit M;Burlet-Schiltz O;Lamond AI;Fort P;Boulon S;Bousquet MP;Coux O
20 S蛋白酶体是控制细胞中蛋白质水平和完整性的关键因素。为了执行其多种功能，它与一系列调节器一起工作，其中包括称为PA 28 γ的核复合物。特别是，PA 28 γ参与细胞增殖和核动力学的调节。我们描述了一种蛋白质PIP 30/FAM 192 A的特征，该蛋白质与PA 28 γ紧密结合，有利于其与20 S蛋白酶体的相互作用，同时抑制其与卷曲蛋白（核Cajal体的中心组分）的结合。因此，PIP 30/FAM 192 A关键地控制相互作用组，并因此控制PA 28 γ的功能，并且似乎是细胞核中细胞内蛋白质稳态的精细调节中的先前未鉴定的参与者。PA 28 γ是20 S蛋白酶体的核激活剂，参与调节几种重要的细胞过程，如细胞增殖、凋亡、核动力学和细胞应激反应。与特异性识别泛素化蛋白的蛋白酶体的19 S调节剂不同，PA 28 γ以ATP和泛素非依赖性方式促进蛋白酶体对几种底物的降解。然而，其确切的行动机制尚不清楚，可能涉及更多的伙伴，这些伙伴仍有待确定。本文报道了PA 28 γ的一个辅因子PIP 30/FAM 192 A的鉴定。PIP 30通过其C-末端直接特异性结合，并通过酪蛋白激酶2磷酸化稳定的相互作用与游离和20 S蛋白酶体相关的PA 28 γ结合。其向含有蛋白酶体的复合物的募集依赖于PA 28 γ，并且其表达增加了PA 28 γ与细胞中20 S蛋白酶体的缔合。对其可能作用的进一步分析表明，PIP 30在体外改变了20 S蛋白酶体对肽降解的PA 28 γ依赖性活化，并通过抑制其与关键Cajal体组分卷曲蛋白的结合来负控制细胞中Cajal体中PA 28 γ的存在。综上所述，我们的数据表明，PIP 30深刻影响PA 28 γ与细胞蛋白质（包括20 S蛋白酶体）的相互作用，表明它是细胞中PA 28 γ的重要调节剂，因此是控制细胞核内蛋白酶体多种功能的新参与者。
The 20S proteasome is a key actor of the control of protein levels and integrity in cells. To perform its multiple functions, it works with a series of regulators, among which is a nuclear complex called PA28γ. In particular, PA28γ participates in the regulation of cell proliferation and nuclear dynamics. We describe here the characterization of a protein, PIP30/FAM192A, which binds tightly to PA28γ and favors its interaction with the 20S proteasome while inhibiting its association with coilin, a central component of nuclear Cajal bodies. Thus, PIP30/FAM192A critically controls the interactome and, consequently, the functions of PA28γ, and appears to be a previously unidentified player in the fine regulation of intracellular proteostasis in the cell nucleus. PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28γ, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28γ. Its recruitment to proteasome-containing complexes depends on PA28γ and its expression increases the association of PA28γ with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28γ-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28γ in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28γ interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28γ in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus.
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影响因子：
7.8
作者：
CARMOFONSECA, M;FERREIRA, J;LAMOND, AI
通讯作者：
LAMOND, AI
影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
3.8
作者：
He J;Cui L;Zeng Y;Wang G;Zhou P;Yang Y;Ji L;Zhao Y;Chen J;Wang Z;Shi T;Zhang P;Chen R;Li X
通讯作者：
Li X
影响因子：
4.4
作者：
Craig, R;Cortens, JP;Beavis, RC
通讯作者：
Beavis, RC
影响因子：
7
作者：
Fabre, Bertrand;Lambour, Thomas;Bousquet-Dubouch, Marie-Pierre
通讯作者：
Bousquet-Dubouch, Marie-Pierre