Studies in metabolism
and cancer have characterized changes in core pathways involving glucose and
glutamine, emphasizing the provision of substrates for building cell mass. But
recent findings suggest that pathways previously considered peripheral may play
a critical role providing mechanisms for cell regulation. Several of these
mechanisms involve the metabolism of non-essential amino acids, for example,
the channeling of glycolytic intermediates into the serine pathway for
one-carbon transfers. Historically, we proposed that the proline biosynthetic
pathway participated in a metabolic interlock with glucose metabolism. The
discovery that proline degradation is activated by p53 directed our attention
to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however,
we find that the biosynthetic mechanisms and the metabolic interlock may depend
on the pathway from glutamine to proline, and it is markedly activated by the
oncogene MYC. These findings add a new dimension to the proline regulatory axis
in cancer and present attractive potential targets for cancer treatment.
Source: The proline regulatory axis
and cancer. Phang JM (phangj@mail.nih.gov),
Liu W, Hancock C, Christian KJ. Front Oncol. 2012;2:60.
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