Growth controls connect: interactions between c-myc and the tuberous sclerosis complex-mTOR pathway.
Among other signals, cell growth is particularly controlled by the target of rapamycin (TOR) pathway that includes the tuberous sclerosis complex genes (TSC1/2), and through transcriptional effects regulated by c-myc. Overexpression of Drosophila Myc and TSC1/2 cause opposing growth and proliferation defects. Despite this relationship, direct regulatory connections between Myc and the TSC have only recently been evaluated. Other than studies of p53 regulation, little consideration has been given to transcriptional regulation of the TSC genes. Here we review evidence that transcriptional controls are potentially important regulators of TSC2 expression, and that Myc is a direct repressor of its expression. Since tuberin loss de-represses Myc protein, the connection between these two growth regulators is positioned to act as a feed-forward loop that would amplify the oncogenic effects of decreased tuberin or increased Myc. Further experiments will be needed to clarify the mechanisms underlying this important connection, and evaluate its overall contribution to cancers caused by TSC loss or Myc gain.
Schmidt
Emmett V
EV
Cancer Research Center at Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA. Schmidt@helix.mgh.harvard.edu
Ravitz
Michael J
MJ
Chen
Li
L
Lynch
Mary
M