SCYL1BP1 modulates neurite outgrowth and regeneration by regulating the Mdm2/p53 pathway.
SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing a protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is required for neurite outgrowth and regeneration. Here we present evidence that SCYL1BP1 inhibits nerve growth factor-mediated neurite outgrowth in PC12 cells and affects morphogenesis of primary cortical neurons by strongly decreasing the p53 protein level in vitro, all of which depends on SCYL1BP1's transcriptional activator domain. Exogenous p53 rescues neurite outgrowth and neuronal morphogenesis defects caused by SCYL1BP1. Furthermore, SCYL1BP1 can directly induce Mdm2 transcription, whereas inhibiting the function of Mdm2 by specific small interfering RNAs results in partial rescue of neurite outgrowth and neuronal morphogenesis defects induced by SCYL1BP1. In vivo experiments show that SCYL1BP1 can also depress axonal regeneration, whereas inhibiting the function of SCYL1BP1 by specific short hairpin RNA enhances it. Taken together, these data strongly suggested that SCYL1BP1 is a novel transcriptional activator in neurite outgrowth by directly modulating the Mdm2/p53-dependent pathway, which might play an important role in CNS development and axonal regeneration after injury.
Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
Yonghua
Y
Liu
Ying
Y
Chen
Xiang
X
Lu
Youhua
Y
Wang
Yinong
Y
Duan
Chun
C
Cheng
Aiguo
A
Shen
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016716:PC12 Cells; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C531983:Scyl1 protein, rat; D016159:Tumor Suppressor Protein p53; D020932:Nerve Growth Factor; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2