PMID- 15134336 OWN - NLM STAT- MEDLINE DCOM- 20040621 LR - 20061115 IS - 1431-6730 (Print) IS - 1431-6730 (Linking) VI - 385 IP - 3-4 DP - 2004 Mar-Apr TI - Visualization of the three-dimensional organization of hypoxia-inducible factor-1 alpha and interacting cofactors in subnuclear structures. PG - 231-7 AB - Cells need oxygen (O2) to meet their metabolic demands. Highly efficient systems of O2-sensing have evolved to initiate responses enabling cells to adapt their metabolism to reduced O2 availability. Of central importance is the activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor complex that controls the expression of genes the products of which regulate glucose uptake and metabolism, vasotonus and angiogenesis, oxygen capacity of the blood as well as cell growth and death. Activation of HIF-1 requires the accumulation and nuclear translocation of the HIF-1alpha subunit, its dimerization with HIF-1beta and the binding of co-activator proteins such as p300. In this study we investigated the three-dimensional (3D) distribution of HIF-1alpha within the nucleus and assigned its localization to known nuclear compartments. Using two-photon microscopy we determined the colocalization of HIF-1alpha and -beta subunits within nuclear domains as well as overlaps between HIF-1alpha and p300. Our data provide information on the nuclear distribution of HIF-1alpha with respect to subnuclear domains that could serve as specific locations for hypoxia-induced gene expression. FAU - Berchner-Pfannschmidt, Utta AU - Berchner-Pfannschmidt U AD - Institut fur Physiologie, Universitat Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany. FAU - Wotzlaw, Christoph AU - Wotzlaw C FAU - Merten, Evelyne AU - Merten E FAU - Acker, Helmut AU - Acker H FAU - Fandrey, Joachim AU - Fandrey J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Biol Chem JT - Biological chemistry JID - 9700112 RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Nuclear Proteins) RN - 0 (Protein Subunits) RN - 0 (Transcription Factors) SB - IM MH - Cell Line, Tumor MH - Cell Nucleus/*chemistry MH - Fluorescent Antibody Technique, Indirect MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Image Processing, Computer-Assisted/*methods MH - Imaging, Three-Dimensional/*methods MH - Microscopy, Fluorescence, Multiphoton/methods MH - Nuclear Proteins/analysis/chemistry MH - Protein Subunits/analysis/*chemistry MH - Transcription Factors/analysis/*chemistry EDAT- 2004/05/12 05:00 MHDA- 2004/06/24 05:00 CRDT- 2004/05/12 05:00 PHST- 2004/05/12 05:00 [pubmed] PHST- 2004/06/24 05:00 [medline] PHST- 2004/05/12 05:00 [entrez] AID - 10.1515/BC.2004.017 [doi] PST - ppublish SO - Biol Chem. 2004 Mar-Apr;385(3-4):231-7. doi: 10.1515/BC.2004.017.