Details

Autor(en) / Beteiligte

• Madan, Esha
• Parker, Taylor M
• Pelham, Christopher J
• Palma, Antonio M
• Peixoto, Maria L
• Nagane, Masaki
• Chandaria, Aliya
• Tomás, Ana R
• Canas-Marques, Rita
• Henriques, Vanessa
• Galzerano, Antonio
• Cabral-Teixeira, Joaquim
• Selvendiran, Karuppaiyah
• Kuppusamy, Periannan
• Carvalho, Carlos
• Beltran, Antonio
• Moreno, Eduardo
• Pati, Uttam K
• Gogna, Rajan

Titel

HIF-transcribed p53 chaperones HIF-1α

Ist Teil von

• Nucleic acids research, 2019-11, Vol.47 (19), p.10212-10234

Ort / Verlag

England

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Chronic hypoxia is associated with a variety of physiological conditions such as rheumatoid arthritis, ischemia/reperfusion injury, stroke, diabetic vasculopathy, epilepsy and cancer. At the molecular level, hypoxia manifests its effects via activation of HIF-dependent transcription. On the other hand, an important transcription factor p53, which controls a myriad of biological functions, is rendered transcriptionally inactive under hypoxic conditions. p53 and HIF-1α are known to share a mysterious relationship and play an ambiguous role in the regulation of hypoxia-induced cellular changes. Here we demonstrate a novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter. In hypoxic cells, this HIF-1α-induced p53 is transcriptionally inefficient but is abundantly available for protein-protein interactions. Further, both WT and MT p53 proteins bind and chaperone HIF-1α to stabilize its binding at its downstream DNA response elements. This p53-induced chaperoning of HIF-1α increases synthesis of HIF-regulated genes and thus the efficiency of hypoxia-induced molecular changes. This basic biology finding has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.