title: Transcription factor SCIRR69 involved in the activation of brain-derived neurotrophic factor gene promoter II in mechanically injured neurons.
abstract: The spinal cord injury and regeneration-related gene #69 (SCIRR69), which was identified in our screen for genes upregulated after spinal cord injury, encode a protein belonging to the cAMP response element-binding protein (CREB)/ATF family of transcription factors. Our previous study showed that SCIRR69 functions as a transcriptional activator. However, the target gene regulated by SCIRR69 and its roles in injured neurons remain unknown. In this study, we showed that SCIRR69 is widely distributed in the central nervous system. Full-length SCIRR69 is an endoplasmic reticulum-bound protein. Following mechanical injury to neurons, SCIRR69 was induced and proteolytically cleaved by site-1 and site-2 proteases, and the proteolytically cleaved SCIRR69 (p60-SCIRR69) was translocated to the nucleus where it bound to brain-derived neurotrophic factor (BDNF) gene promoter II. In addition, loss- and gain-of-function studies confirmed that SCIRR69 is involved in the regulation of BDNF expression in injured neurons. As expected, the culture supernatants of PC12 cells stably expressing p60-SCIRR69 contained higher levels of BDNF, and more remarkably promoted neurite outgrowth in a spinal cord slice culture model in vitro than the supernatants of control cells. These results suggest that SCIRR69 is a novel regulator of the BDNF gene and may play an important role in the repair and/or regeneration of damaged neural tissues by specifically activating BDNF promoter II.
authors.affiliation: State Key Laboratory of Proteomics, Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Haiping
authors.initials: H
authors.lastname: Que
authors.forename: Zhenlian
authors.initials: Z
authors.lastname: Ma
authors.forename: Shuguang
authors.initials: S
authors.lastname: Yang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ni
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Luo
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yang
authors.forename: Shuqian
authors.initials: S
authors.lastname: Jing
authors.forename: Shaojun
authors.initials: S
authors.lastname: Liu
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D016384:Consensus Sequence; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000648:ultrastructure; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014161:Transduction, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C576348:Creb3l2 protein, rat; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors