Abstract
Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL-/- renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 237-246 |
| Number of pages | 10 |
| Journal | Cancer Cell |
| Volume | 1 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology
Cite this
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. / Kondo, Keiichi; Klco, Jeff; Nakamura, Eijiro; Lechpammer, Mirna; Kaelin, William G.
In: Cancer Cell, Vol. 1, No. 3, 04.2002, p. 237-246.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
AU - Kondo, Keiichi
AU - Klco, Jeff
AU - Nakamura, Eijiro
AU - Lechpammer, Mirna
AU - Kaelin, William G.
PY - 2002/4
Y1 - 2002/4
N2 - Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL-/- renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo.
AB - Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL-/- renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0036528246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036528246&partnerID=8YFLogxK
U2 - 10.1016/S1535-6108(02)00043-0
DO - 10.1016/S1535-6108(02)00043-0
M3 - Article
VL - 1
SP - 237
EP - 246
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 3
ER -