Identification of regions critical for the integrity of the TSC1-TSC2-TBC1D7 complex

PLoS One. 2014 Apr 8;9(4):e93940. doi: 10.1371/journal.pone.0093940. eCollection 2014.

Abstract

The TSC1-TSC2-TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues. Inactivating TSC1 and TSC2 mutations cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterised by the occurrence of benign tumours in various organs and tissues, notably the brain, skin and kidneys. TBC1D7 mutations have not been reported in TSC patients but homozygous inactivation of TBC1D7 causes megaencephaly and intellectual disability. Here, using an exon-specific deletion strategy, we demonstrate that some regions of TSC1 are not necessary for the core function of the TSC1-TSC2 complex. Furthermore, we show that the TBC1D7 binding site is encoded by TSC1 exon 22 and identify amino acid residues involved in the TSC1-TBC1D7 interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Exons
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mutation
  • Tuberous Sclerosis / genetics*
  • Tuberous Sclerosis / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • TBC1D7 protein, human
  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins

Grant support

The study was supported by the Department of Clinical Genetics, Erasmus MC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.