The von Hippel-Lindau tumor suppressor targets to mitochondria.
Subcellular localization of von Hippel-Lindau (VHL) tumor suppressor may clarify its role in tumorigenesis. In rat kidney, we observed a granular cytoplasmic immunostaining of VHL, as seen in human tissues. The green fluorescent protein (GFP)-tagged VHL also appeared as cytoplasmic granules in vitro and was colocalized with a mitochondrion-selective dye. Immunogold electron microscopy localized VHL specifically to the mitochondrion. Mitochondria retaining GFP-VHL fusion protein, mimicking an insertional VHL mutant, displayed abnormal phenotypes. Among these, small mitochondria have been observed in clear cell renal carcinomas known to have frequent VHL alterations. Thus, VHL may contribute to tumorigenesis through mitochondria-based action.
Shiao
Y H
YH
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, NIH, Maryland 21702, USA. shiao@mail.ncifcrf.gov
Resau
J H
JH
Nagashima
K
K
Anderson
L M
LM
Ramakrishna
G
G
D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008025:Ligases; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D010957:Plasmids; D014176:Protein Biosynthesis; D051381:Rats; D014162:Transfection; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D008164:Luminescent Proteins; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases