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TLX controls angiogenesis through interaction with the von Hippel-Lindau protein
- Source :
- Biology Open, Vol 1, Iss 6, Pp 527-535 (2012)
- Publication Year :
- 2012
- Publisher :
- The Company of Biologists, 2012.
-
Abstract
- Summary TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) for binding to pVHL, which contributes to the stabilization of HIF-2α in neuroblastoma during normoxia. Upon hypoxia, TLX increases in the nucleus where it binds in close proximity of the HIF-response element on the VEGF-promoter chromatin, and, together with HIF-2α, recruits RNA polymerase II to induce VEGF expression. Conversely, depletion of TLX by shRNA decreases the expression of HIF-2α and VEGF as well as the growth-promoting and colony-forming capacity of the neuroblastoma cell lines IMR-32 and SH-SY5Y. On the contrary, silencing HIF-2α will slightly increase TLX, suggesting that TLX acts to maintain a hypoxic environment when HIF-2α is decreasing. Our results demonstrate TLX to play a key role in controlling angiogenesis by regulating HIF-2α. TLX and pVHL might counterbalance each other in important fate decisions such as self-renewal and differentiation, as well as angiogenesis and anti-angiogenesis.
- Subjects :
- TLX
VHL
HIF-2α
Angiogenesis
Neuroblastoma
Science
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 20466390
- Volume :
- 1
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Biology Open
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9e1d07fdd7ad47bd9c8367ab22d413cb
- Document Type :
- article
- Full Text :
- https://doi.org/10.1242/bio.2012893