PUBLICATION
PRAJA is overexpressed in glioblastoma and contributes to neural precursor development
- Authors
- Shin, J., Mishra, V., Glasgow, E., Zaidi, S., Ohshiro, K., Chitti, B., Kapadia, A.A., Rana, N., Mishra, L., Deng, C.X., Rao, S., Mishra, B.
- ID
- ZDB-PUB-171003-3
- Date
- 2017
- Source
- Genes & Cancer 8: 640-649 (Journal)
- Registered Authors
- Glasgow, Eric
- Keywords
- PRAJA, apoptosis, glioblastoma
- MeSH Terms
- none
- PubMed
- 28966725 Full text @ Genes Cancer
Citation
Shin, J., Mishra, V., Glasgow, E., Zaidi, S., Ohshiro, K., Chitti, B., Kapadia, A.A., Rana, N., Mishra, L., Deng, C.X., Rao, S., Mishra, B. (2017) PRAJA is overexpressed in glioblastoma and contributes to neural precursor development. Genes & Cancer. 8:640-649.
Abstract
PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the developing brain through loss of function studies, using morpholinos targeting Praja1 in embryonic zebrafish, and observed that Praja1 is expressed prominently in regions enriched with neural precursor cell subtypes. Antisense Praja morpholinos resulted in multiple embryonic defects including delayed neural development likely through increased apoptosis. Further studies revealed high levels of Cdk1 with loss of Praja1 in TGF-β or insulin treated cells, supporting the link between Praja1 and cell cycle regulation. In summary, these studies underscore Praja's role in mammalian brain development and Praja1 deregulation may lead to gliomas possibly through the regulation of cell cycle and/or apoptosis.
Errata / Notes
This article is corrected by ZDB-PUB-220906-90 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping