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PML inhibits HIF-1a translation and neoangiogenesis through repression of mTOR

最後更新日期 : 2015-08-25

PML inhibits Hif-1αtranslation and neoangiogenesis through repression of mTOR

 

Nature 442, 779-785 (17 Aug 2006)

 

Speaker傅孝瑜                              Date2006/11/8, 14:10~15:00

Commentator:凌斌 老師                      PlaceRoom601

 

Abstract

Promyelocytic leukemia (PML) gene is known as a tumor suppressor. Several human cancers such as small cell lung carcinoma are associated with loss of PML. Observed in past research, forced PML expression induces growth inhibition, apoptosis and cellular senescence(1). Since neoangiogenesis is the proliferation of network of blood vessels that plays an important role in tumor progression and poor prognosis. The authors tried to find out weather PML regulates neoangiogenesis and how it works. They demonstrate that pml opposes revascularization upon ischaemia by negative regulation of Hif-1α whose target gene is VEGF by comparing Pml-/- and wild-type mice and mouse embryonic fibroblast (MEF). Furthermore, PML controls Hif-1α accumulation in hypoxia condition in a mTOR-dependent, TSC2/REDD-independent manner found by analyzing (mammalian target of rapamycin) activity and phosphorylation of S6 kinase on amino acid T389, the major rapamycin-sensitive site. The authors use tumorigenesis assays with transformed MEFs to study the role of Pml in regulating tumor angiogenesis. Then the results show PML antagonizes tumor angiogenesis as a novel suppressor of mTOR and neoangiogenesis.

 

References

1.      Salomoni, P. & Pandolfi, P.P. The role of PML in tumor suppression. Cell 108, 165-170(2002).

2.      Brugarolas, J. et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 18, 2893–-2904 (2004).

期刊名稱: Nature 442: 779-785, 2006
文章名稱: PML inhibits HIF-1a translation and neoangiogenesis through repression of mTOR
講者: 傅孝瑜
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