Aberrant beta-catenin signaling in tuberous sclerosis

Related Experiment Video

Updated: Aug 17, 2026

Label-Free Non-Linear Optics for the Study of Tubulin-Dependent Defects in Central Myelin
08:07

Label-Free Non-Linear Optics for the Study of Tubulin-Dependent Defects in Central Myelin

Published on: March 24, 2023

Baldwin C Mak1, Heidi L Kenerson, Lauri D Aicher

  • 1Department of Surgery, University of Washington, 1959 NE Pacific St., Box 356410, Seattle, WA 98195, USA.

The American Journal of Pathology
|June 24, 2005
PubMed

Insights

Tuberous sclerosis complex (TSC) involves abnormal beta-catenin signaling, impacting Wnt pathway activity. This study reveals GSK3

Area of Science:

  • Cellular biology
  • Molecular biology
  • Oncology

Background:

  • Tuberous sclerosis complex (TSC) pathology involves diverse phenotypes linked to aberrant signaling pathways.
  • The TSC1/TSC2 protein complex negatively regulates mTOR and influences beta-catenin signaling.
  • Previous in vitro studies indicated TSC1/TSC2 complex association with beta-catenin degradation machinery.

Purpose of the Study:

  • To investigate the role of beta-catenin signaling in TSC pathogenesis in vivo.
  • To elucidate the interaction between the TSC1/TSC2 complex and the beta-catenin degradation complex under Wnt stimulation.
  • To explore the influence of GSK3 activity on the TSC1/TSC2 complex.

Main Methods:

  • Analysis of beta-catenin and its effectors (cyclin D1, connexin 43) in TSC-related angiomyolipomas and lymphangioleiomyomatosis.
  • Assessment of Wnt signaling inhibition by disease-causing TSC2 mutants.
  • Investigation of TSC1/TSC2 complex interactions with GSK3 and Axin under varying Wnt conditions.
  • Evaluation of GSK3 inhibition (lithium chloride) and TSC1 phosphorylation site disruption effects on complex stability and interactions.

Main Results:

  • Beta-catenin and its downstream effectors, cyclin D1 and connexin 43, are upregulated in TSC-related tumors.
  • Disease-causing TSC2 mutants fail to inhibit Wnt signaling, confirming pathway dysregulation.
  • TSC1/TSC2 complex interaction dynamics with beta-catenin degradation components are modulated by Wnt stimulation.
  • GSK3 activity is crucial for the assembly and stability of the beta-catenin degradation complex, and its modulation impacts TSC1/TSC2 complex integrity.

Conclusions:

  • Beta-catenin signaling is implicated in TSC pathogenesis in vivo.
  • The TSC1/TSC2 complex modulates Wnt/beta-catenin signaling through interaction with the degradation complex.
  • GSK3 plays a novel role in regulating the TSC1/TSC2 complex via TSC1 phosphorylation.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

Microtubules in Signaling01:22

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...