Identification and characterization of new isoforms of human fas apoptotic inhibitory molecule (FAIM).
Identification and characterization of new isoforms of human fas apoptotic inhibitory molecule (FAIM).
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DOI：
10.1371/journal.pone.0185327
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Pérez-García MJ
中科院分区：
文献类型：
--
作者：
Coccia E;Calleja-Yagüe I;Planells-Ferrer L;Sanuy B;Sanz B;López-Soriano J;Moubarak RS;Munell F;Barneda-Zahonero B;Comella JX;Pérez-García MJ
Fas凋亡抑制分子（fam）是一种进化上高度保守的死亡受体拮抗剂，广泛表达并参与生理和病理过程。迄今为止，已经确定了两种FAIM转录变体，即FAIM短（FAIM- s）和FAIM长（FAIM- l）。FAIM-S在免疫系统中普遍表达，是一种抗凋亡蛋白。此外，在神经元中，该亚型通过NF-кB和ERK信号传导促进ngf诱导的神经突生长。相反，FAIM-L仅在神经元中发现，在那里它对几种刺激发挥抗凋亡活性。除了这两种变体之外，计算机研究还指出存在另外两种异构体，但迄今为止都没有对其进行表征。在这方面，我们在这里证实了人类胎儿大脑、胎儿和成人睾丸以及胎盘组织中存在这两种额外的FAIM亚型。我们将它们命名为FAIM-S_2a和FAIM-L_2a，因为它们与FAIM-S和FAIM-L具有相同的序列，但包括外显子2a。PCR和western blot结果显示，FAIM-S_2a在所有被测组织和细胞模型中普遍表达，而FAIM-L_2a仅在神经系统组织中表达。此外，我们发现，当剪接因子nSR100在非神经元细胞中过表达时，可以诱导神经元亚型的表达，从而确定它与fam - l和fam - l_2a的产生有关。在功能上，FAIM-S_2a和FAIM-L_2a在神经元模型中响应NGF刺激增加了神经突起的生长。因此，这一观察结果支持了这两种亚型参与神经元分化的观点。此外，亚细胞分离实验显示，与FAIM-S和FAIM-L相比，FAIM-S_2a和FAIM-L_2a能够定位到细胞核，在那里它们可能具有额外的功能。综上所述，本文报道了两种可能在神经系统的生理和病理中起相关作用的新型fam亚型。
Fas Apoptosis Inhibitory Molecule (FAIM) is an evolutionarily highly conserved death receptor antagonist, widely expressed and known to participate in physiological and pathological processes. Two FAIM transcript variants have been characterized to date, namely FAIM short (FAIM-S) and FAIM long (FAIM-L). FAIM-S is ubiquitously expressed and serves as an anti-apoptotic protein in the immune system. Furthermore, in neurons, this isoform promotes NGF-induced neurite outgrowth through NF-кB and ERK signaling. In contrast FAIM-L is found only in neurons, where it exerts anti-apoptotic activity against several stimuli. In addition to these two variants, in silico studies point to the existence of two additional isoforms, neither of which have been characterized to date. In this regard, here we confirm the presence of these two additional FAIM isoforms in human fetal brain, fetal and adult testes, and placenta tissues. We named them FAIM-S_2a and FAIM-L_2a since they have the same sequence as FAIM-S and FAIM-L, but include exon 2a. PCR and western blot revealed that FAIM-S_2a shows ubiquitous expression in all the tissues and cellular models tested, while FAIM-L_2a is expressed exclusively in tissues of the nervous system. In addition, we found that, when overexpressed in non-neuronal cells, the splicing factor nSR100 induces the expression of the neuronal isoforms, thus identifying it as responsible for the generation of FAIM-L and FAIM-L_2a. Functionally, FAIM-S_2a and FAIM-L_2a increased neurite outgrowth in response to NGF stimulation in a neuronal model. This observation thus, supports the notion that these two isoforms are involved in neuronal differentiation. Furthermore, subcellular fractionation experiments revealed that, in contrast to FAIM-S and FAIM-L, FAIM-S_2a and FAIM-L_2a are able to localize to the nucleus, where they may have additional functions. In summary, here we report on two novel FAIM isoforms that may have relevant roles in the physiology and pathology of the nervous system.
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影响因子：
9
作者：
Huo J;Ma Y;Liu JJ;Ho YS;Liu S;Soh LY;Chen S;Xu S;Han W;Hong A;Lim SC;Lam KP
通讯作者：
Lam KP
死亡受体拮抗剂FAIM通过依赖ERK和NF-KAPP B信号传导的机制促进神经突生长。
影响因子：
7.8
作者：
Sole, Carme;Dolcet, Xavier;Segura, Miguel F;Gutierrez, Humberto;Diaz-Meco, Maria-Teresa;Gozzelino, Raffaella;Sanchis, Daniel;Bayascas, Jose R;Gallego, Carme;Moscat, Jorge;Davies, Alun M;Comella, Joan X
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Comella, Joan X
影响因子：
4.6
作者：
Martínez-Mármol R;Barneda-Zahonero B;Soto D;Andrés RM;Coccia E;Gasull X;Planells-Ferrer L;Moubarak RS;Soriano E;Comella JX
通讯作者：
Comella JX
影响因子：
7.2
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通讯作者：
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影响因子：
7.7
作者：
Li Q;Zheng S;Han A;Lin CH;Stoilov P;Fu XD;Black DL
通讯作者：
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