XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
MOLECULar MECHaNISMS INvOLvED IN rESPONSE TO HYPOXIa
Juraj Kopáček, Jaromír Pastorek and Silvia Pastoreková
Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9,
845 05 Bratislava
Cellular responses to diminished supply of oxygen include growth arrest, apoptosis,
anaerobic glycolysis, angiogenesis etc. The primary response to the lack of oxygen at
the molecular level is the stabilization of a subunit of HIF-1 transcriptional complex,
a key regulator of the genes involved in adaptation to the hypoxic stress. In normoxia,
HIF-1a undergoes hydroxylation that is required for its interaction with the product of
the with type von Hippel-Lindau (VHL) tumor suppressor gene. This interaction results in
fast ubiquitilation and proteasome degradation of HIF-1a. Loss or mutation in VHL, the
main negative regulator of the hypoxic pathway, leads to development of the hypoxic
phenotype also under normoxic conditions. In addition, stabilization of HIF-1a could be
achieved by signal transduction through the pathways regulated by activated oncogenes
that can contribute to or amplify the effects of of HIF-1 transcriptional complex. HIF-1 is
a key regulator of a broad range of cellular and systemic responses to hypoxia and acts
in all mammalian cells. HIF-1 activity is dependent upon the availability of the HIF-1α
subunit, which is in turn regulated by cellular oxygen levels.
This work was supported by the Research & Development Operational Programme funded
by the ERDF „TRANSMED” and by VEGA 2/0194/09.
68 XXII. Biochemistry Congress, Martin