Letter abstract
Nature Cell Biology 10, 611 - 618 (2008)
Published online: 6 April 2008 | doi:10.1038/ncb1724
p53 regulates glucose metabolism through an IKK-NF-
B pathway and inhibits cell transformation
Keiko Kawauchi1, Keigo Araki1, Kei Tobiume1 & Nobuyuki Tanaka1
Cancer cells use aerobic glycolysis preferentially for energy provision1, 2 and this metabolic change is important for tumour growth3, 4. Here, we have found a link between the tumour suppressor p53, the transcription factor NF-
B and glycolysis. In p53-deficient primary cultured cells, kinase activities of IKK
and IKK
and subsequent NF-B activity were enhanced. Activation of NF-B, by loss of p53, caused an increase in the rate of aerobic glycolysis and upregulation of Glut3. Oncogenic Ras-induced cell transformation and acceleration of aerobic glycolysis in p53-deficient cells were suppressed in the absence of p65/NF-B expression, and were restored by GLUT3 expression. It was also shown that a glycolytic inhibitor diminished the enhanced IKK activity in p53-deficient cells. Moreover, in Ras-expressing p53-deficient cells, IKK activity was suppressed by p65 deficiency and restored by GLUT3 expression. Taken together, these data indicate that p53 restricts activation of the IKK–NF-B pathway through suppression of glycolysis. These results suggest that a positive-feedback loop exists, whereby glycolysis drives IKK–NF-B activation, and that hyperactivation of this loop by loss of p53 is important in oncogene-induced cell transformation.
- Department of Molecular Oncology, Institute of Gerontology, Nippon Medical School, Kosugi-cho 1-396, Nakahara-ku, Kawasaki-shi, Kanagawa 211-8533, Japan.
Correspondence to: Nobuyuki Tanaka1 e-mail: nobuta@nms.ac.jp
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