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| Pàgina inicial > Articles > Articles publicats > Identification and characterization of new isoforms of human fas apoptotic inhibitory molecule (FAIM) |
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Department of Pathology. NYU Langone Medical Center) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
| Data: | 2017 |
| Resum: | 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. |
| Ajuts: | Ministerio de Economía y Competitividad SAF2013-47989-R Ministerio de Economía y Competitividad SAF2016-80236-R Ministerio de Economía y Competitividad CIBERNED CB06/05/1104 Ministerio de Economía y Competitividad PIE13/00027 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR1609 |
| Nota: | Altres ajuts: La Marató de TV3 (201414-30); Fellowship BES-2014-069550 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Alternative Splicing ; Animals ; Apoptosis Regulatory Proteins ; Cell Line ; Exons ; Humans ; Nucleic Acid Conformation ; PC12 Cells ; Protein Isoforms ; Protein Stability ; Rats ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Thermodynamics |
| Publicat a: | PloS one, Vol. 12 Núm. 10 (october 2017) , p. e0185327, ISSN 1932-6203 |
