Smurfs in Protein Homeostasis, Signaling, and Cancer.
Smurfs in Protein Homeostasis, Signaling, and Cancer.
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DOI：
10.3389/fonc.2018.00295
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发表时间：
2018
影响因子：
4.7
通讯作者：
Blank M
中科院分区：
文献类型：
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作者：
Koganti P;Levy-Cohen G;Blank M
蛋白质泛素化是一种进化保守的高度协调的酶级联反应，对正常细胞功能和稳态维持至关重要。该途径依赖于一组确定的细胞酶，其中包括底物特异性E3泛素连接酶（E3）。这些连接酶是最关键的参与者，因为它们定义了泛素化的时空性质，并赋予这种级联反应特异性。Smurf 1和Smurf 2（Smurfs）是C2-WW-HECT-结构域E3泛素连接酶，其最近成为关键细胞过程的重要决定因素。这些过程包括细胞增殖和分化、染色质组织和动力学、DNA损伤反应和基因组完整性维持、基因表达、细胞干细胞性、迁移和侵袭。所有这些过程都密切相关，并在癌症中发生深刻变化。最初，Smurf蛋白被鉴定为骨形态发生蛋白（BMP）和转化生长因子β（TGF-β）信号通路的负调节因子。然而，最近的研究已经将蓝精灵的生物学功能范围扩展到BMP/TGF-β信号调节之外。在这里，我们提供了一个关键的文献综述和蓝精灵在分子和细胞生物学中的调节作用的更新，重点是癌症。我们还强调了研究表明Smurf蛋白对肿瘤细胞对抗癌疗法的敏感性的影响。进一步深入分析蓝精灵的生物学功能和对分子通路的影响，可以为癌症的诊断和治疗提供新的治疗靶点和范例。
Protein ubiquitination is an evolutionary conserved highly-orchestrated enzymatic cascade essential for normal cellular functions and homeostasis maintenance. This pathway relies on a defined set of cellular enzymes, among them, substrate-specific E3 ubiquitin ligases (E3s). These ligases are the most critical players, as they define the spatiotemporal nature of ubiquitination and confer specificity to this cascade. Smurf1 and Smurf2 (Smurfs) are the C2-WW-HECT-domain E3 ubiquitin ligases, which recently emerged as important determinants of pivotal cellular processes. These processes include cell proliferation and differentiation, chromatin organization and dynamics, DNA damage response and genomic integrity maintenance, gene expression, cell stemness, migration, and invasion. All these processes are intimately connected and profoundly altered in cancer. Initially, Smurf proteins were identified as negative regulators of the bone morphogenetic protein (BMP) and the transforming growth factor beta (TGF-β) signaling pathways. However, recent studies have extended the scope of Smurfs' biological functions beyond the BMP/TGF-β signaling regulation. Here, we provide a critical literature overview and updates on the regulatory roles of Smurfs in molecular and cell biology, with an emphasis on cancer. We also highlight the studies demonstrating the impact of Smurf proteins on tumor cell sensitivity to anticancer therapies. Further in-depth analyses of Smurfs' biological functions and influences on molecular pathways could provide novel therapeutic targets and paradigms for cancer diagnosis and treatment.
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影响因子：
--
作者：
Chandhoke AS;Chanda A;Karve K;Deng L;Bonni S
通讯作者：
Bonni S
影响因子：
11.4
作者：
Butin-Israeli, Veronika;Adam, Stephen A.;Goldman, Anne E.;Goldman, Robert D.
通讯作者：
Goldman, Robert D.
DOI：
10.1073/pnas.1003023107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Chong, P. Andrew;Lin, Hong;Forman-Kay, Julie D.
通讯作者：
Forman-Kay, Julie D.
影响因子：
7.8
作者：
Borroni AP;Emanuelli A;Shah PA;Ilić N;Apel-Sarid L;Paolini B;Manikoth Ayyathan D;Koganti P;Levy-Cohen G;Blank M
通讯作者：
Blank M
影响因子：
82.9
作者：
通讯作者：
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