On the Quest of Cellular Functions of PEA-15 and the Therapeutic Opportunities.
On the Quest of Cellular Functions of PEA-15 and the Therapeutic Opportunities.
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DOI：
10.3390/ph8030455
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发表时间：
2015-07-31
期刊：
影响因子：
--
通讯作者：
Wei Y
中科院分区：
文献类型：
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作者：
Wei Y
星形胶质细胞中富含磷酸蛋白15kda (PEA-15)，这是一种在所有哺乳动物中普遍表达的小蛋白，几十年来，人们一直知道它与各种蛋白伴侣沿着不同的生物学途径进行有效的相互作用。PEA-15最显著的相互作用伙伴包括丝裂原活化蛋白激酶（MAPK）途径中的细胞外信号调节激酶1和2 (ERK1/2)，参与死亡诱导信号复合物（DISC）形成的fas相关死亡结构域（FADD）蛋白，以及影响胰岛素敏感性的磷脂酶D1 （PLD1）。然而，PEA-15的实际细胞功能仍然是一个谜，为什么这种蛋白在几乎所有细胞和组织类型中表达的问题仍然没有答案。在这里，我们综合了PEA-15最近的结构、生物学和临床研究，重点研究了PEA-15的抗凋亡、抗增殖和抗炎特性，并提出了PEA-15在不同细胞类型中维持死亡和生存平衡的保护性作用。在这种微妙的平衡不可持续的情况下，PEA-15可能会变得病态，导致各种疾病，包括癌症和糖尿病。靶向PEA-15相互作用，或使用PEA-15蛋白作为治疗药物，可能为治疗这些疾病提供更广阔的机会。
Phosphoprotein enriched in astrocytes, 15 KDa (PEA-15), a ubiquitously expressed small protein in all mammals, is known for decades for its potent interactions with various protein partners along distinct biological pathways. Most notable interacting partners of PEA-15 include extracellular signal-regulated kinase 1 and 2 (ERK1/2) in the mitogen activated protein kinase (MAPK) pathway, the Fas-associated death domain (FADD) protein involving in the formation of the death-inducing signaling complex (DISC), and the phospholipase D1 (PLD1) affecting the insulin sensitivity. However, the actual cellular functions of PEA-15 are still mysterious, and the question why this protein is expressed in almost all cell and tissue types remains unanswered. Here we synthesize the most recent structural, biological, and clinical studies on PEA-15 with emphases on its anti-apoptotic, anti-proliferative, and anti-inflammative properties, and propose a converged protective role of PEA-15 that maintains the balance of death and survival in different cell types. Under conditions that this delicate balance is unsustainable, PEA-15 may become pathological and lead to various diseases, including cancers and diabetes. Targeting PEA-15 interactions, or the use of PEA-15 protein as therapeutics, may provide a wider window of opportunities to treat these diseases.