Table 1Summarizes E3 ubiquitin ligases involved in process of neurodevelopment and promising molecules that have been shown to modulate their activity and retain possible therapeutic potential.
Figure1 An illustration of orchestration of factors involved in neurodevelopment and neurodegeneration: The upper part of the figure represents how stepwise modifications occur during prenatal period of brain development. As described in respective sections of the text, few crucially important genes, which play pivotal roles at various stages of brain development, have been mentioned at the top. To establish a better understanding, schematic of cellular translation machinery along with other protein quality control systems has also been drawn. A state …show more content…
Functional E6-AP promotes the ubiquitylation of tumor suppressor proteins such as p53 and p27 and regulates cellular proliferation and growth. E6-AP also plays a significant role in the clearance of mutant misfolded proteins linked with various neurodegenerative diseases. (B) Mahogunin functions as a RING finger E3 ubiquitin ligase; and null mutation in mahogunin is linked with spongiform neurodegeneration. Our studies reveal the potential roles of MGRN1 as a QC E3 ubiquitin ligase involved in the elimination of mutated proteins linked with polyglutamine and ALS neurodegenerative diseases. (C) ITCH E3 ubiquitin ligase specifically targets cytoplasmic misfolded proteins for their removal from the dense crowded cellular milieu. The central segment represents overall functional roles of QC E3 ubiquitin ligases due to their crucial involvement in the neurodevelopment and
Figure1 An illustration of orchestration of factors involved in neurodevelopment and neurodegeneration: The upper part of the figure represents how stepwise modifications occur during prenatal period of brain development. As described in respective sections of the text, few crucially important genes, which play pivotal roles at various stages of brain development, have been mentioned at the top. To establish a better understanding, schematic of cellular translation machinery along with other protein quality control systems has also been drawn. A state …show more content…
Functional E6-AP promotes the ubiquitylation of tumor suppressor proteins such as p53 and p27 and regulates cellular proliferation and growth. E6-AP also plays a significant role in the clearance of mutant misfolded proteins linked with various neurodegenerative diseases. (B) Mahogunin functions as a RING finger E3 ubiquitin ligase; and null mutation in mahogunin is linked with spongiform neurodegeneration. Our studies reveal the potential roles of MGRN1 as a QC E3 ubiquitin ligase involved in the elimination of mutated proteins linked with polyglutamine and ALS neurodegenerative diseases. (C) ITCH E3 ubiquitin ligase specifically targets cytoplasmic misfolded proteins for their removal from the dense crowded cellular milieu. The central segment represents overall functional roles of QC E3 ubiquitin ligases due to their crucial involvement in the neurodevelopment and