Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome.

Published

Journal Article

Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.

Full Text

Duke Authors

Cited Authors

  • Corradetti, MN; Inoki, K; Bardeesy, N; DePinho, RA; Guan, K-L

Published Date

  • July 1, 2004

Published In

Volume / Issue

  • 18 / 13

Start / End Page

  • 1533 - 1538

PubMed ID

  • 15231735

Pubmed Central ID

  • 15231735

Electronic International Standard Serial Number (EISSN)

  • 1549-5477

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.1199104

Language

  • eng