Related Experiment Video
Updated: Jan 19, 2026
07:26
Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
2.4K
TWIST1 Heterodimerization with E12 Requires Coordinated Protein Phosphorylation to Regulate Periostin Expression
Svetlana A Mikheeva1,2,3, Nathan D Camp4,5,6, Lei Huang7
1Department of Neurosurgery, Houston Methodist Research Institute, Houston, TX 77030, USA. smikheeva@houstonmethodist.org.
Cancers
|September 22, 2019
Summary
Phosphorylation of TWIST1 (TW) and E12 transcription factors promotes glioblastoma invasion by regulating TWIST1 dimerization and periostin (POSTN) expression. Inhibiting this TWIST1-POSTN signaling offers potential glioblastoma treatment strategies.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Cell Biology
Background:
- Glioblastoma (GBM) invasion into brain tissue significantly worsens patient prognosis.
- The TWIST1 (TW) transcription factor and its target gene periostin (POSTN) are known to drive GBM cell invasion.
- TWIST1 function is modulated by phosphorylation and dimerization.
Purpose of the Study:
- To investigate how serine 68 phosphorylation in TWIST1 affects its dimerization, POSTN expression, and glioma cell invasion.
- To elucidate the role of TWIST1 heterodimerization versus homodimerization in GBM invasion.
Main Methods:
- Generated and analyzed TWIST1 mutants, including a hypophosphorylation mutant (TW(S68A)).
- Utilized forced dimerization constructs (FDCs) for TWIST1:E12 heterodimers and TWIST1:TWIST1 homodimers.
- Assessed glioma cell invasion in vitro and measured POSTN and PDGFRa mRNA expression.
Main Results:
- The TW(S68A) mutant impaired TWIST1 heterodimerization with E12 and reduced glioma cell invasion.
- TWIST1:E12 FDCs enhanced invasion and upregulated POSTN, correlating with cytoskeletal changes.
- TWIST1:TWIST1 homodimer FDCs suppressed POSTN expression and invasion.
- Phosphorylation of TWIST1 (S68) and E12 (S139) coordinately regulated POSTN and PDGFRa mRNA.
Conclusions:
- TWIST1 promotes GBM invasion through phosphorylation-dependent heterodimerization with E12, regulating downstream targets like POSTN.
- Targeting TWIST1-POSTN signaling pathways presents a potential therapeutic strategy for glioblastoma.
Related Concept Videos
01:16TGF - β Signaling Pathway
10.5K
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...
10.5K
01:22PI3K/mTOR/AKT Signaling Pathway
5.4K
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...
5.4K
01:19Cadherins in Tissue Organization
3.9K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.9K
01:19Interactions Between Signaling Pathways
7.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
01:20The JAK-STAT Signaling Pathway
12.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
12.2K
02:33Hedgehog Signaling Pathway
9.8K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.8K