Altered Stra13 and Dec2 circadian gene expression in hypoxic cells
- Universite de Nice-Sophia Antipolis, CNRS FRE3094, 28 Av. Valrose, 06108 Nice (France)
- Universite Paris-Sud, INSERM U776, Hopital Paul Brousse, 14 Av. P.V. Couturier, 94800 Villejuif (France)
- Cell Biology and Stem Cells Unit, CIC BioGUNE, Technologic Park of Bizkaia, 48160-Derio (Spain)
The circadian system regulates rhythmically most of the mammalian physiology in synchrony with the environmental light/dark cycle. Alteration of circadian clock gene expression has been associated with tumour progression but the molecular links between the two mechanisms remain poorly defined. Here we show that Stra13 and Dec2, two circadian transcriptional regulators which play a crucial role in cell proliferation and apoptosis are overexpressed and no longer rhythmic in serum shocked fibroblasts treated with CoCl{sub 2,} a substitute of hypoxia. This effect is associated with a loss of circadian expression of the clock genes Rev-erb{alpha} and Bmal1, and the clock-controlled gene Dbp. Consistently, cotransfection assays demonstrate that STRA13 and DEC2 both antagonize CLOCK:BMAL1 dependent transactivation of the Rev-erb{alpha} and Dbp promoters. Using a transplantable osteosarcoma tumour model, we show that hypoxia is associated with altered circadian expression of Stra13, Dec2, Rev-erb{alpha}, Bmal1 and Dbp in vivo. These observations collectively support the notion that overexpression of Stra13 and Dec2 links hypoxia signalling to altered circadian clock gene expression.
- OSTI ID:
- 21143688
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.03.009; PII: S0006-291X(08)00475-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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