Related Experiment Video

Updated: Feb 25, 2026

Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
10:26

Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions

Published on: December 20, 2017

10.0K

TIE2 Associates with Caveolae and Regulates Caveolin-1 To Promote Their Nuclear Translocation

Mohammad B Hossain1, Rehnuma Shifat2, Jingyi Li2,3

  • 1Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA mbhossain@mdanderson.org cmanzano@mdanderson.org.

Molecular and Cellular Biology
|August 2, 2017
PubMed

Insights

Cancer cells evade radiation therapy via aberrant DNA repair. This study reveals that TIE2 receptor nuclear translocation, crucial for DNA repair, depends on caveolin-1. Inhibiting both TIE2 and caveolin-1 sensitizes glioma cells to radiation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aberrant DNA repair allows cancer cells to resist chemotherapy and radiotherapy.
  • TIE2 receptor nuclear translocation after irradiation aids DNA repair via nonhomologous end-joining.
  • The mechanism of TIE2 endocytosis and nuclear trafficking remained unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism of TIE2 endocytosis and nuclear translocation.
  • To investigate the role of caveolin-1 in TIE2 trafficking.
  • To evaluate the therapeutic potential of targeting TIE2 and caveolin-1 in glioblastoma radiosensitization.

Main Methods:

  • Subcellular fractionation and confocal microscopy to visualize TIE2/caveolin-1 complexes.
  • Inhibitor studies and small interfering RNA (siRNA) knockdown of caveolin-1 and TIE2.
  • In vitro and in vivo phosphorylation assays.
  • Assessment of glioblastoma cell radiosensitization.

Main Results:

  • Irradiation-induced TIE2 trafficking is dependent on caveolin-1, a component of caveolae.
  • TIE2 and caveolin-1 form complexes in the nucleus, essential for DNA repair.
  • TIE2 directly phosphorylates caveolin-1, regulating complex formation and nuclear translocation.
  • Combined inhibition of TIE2 and caveolin-1 significantly radiosensitizes malignant glioma cells.

Conclusions:

  • Caveolin-1 is a key regulator of TIE2 nuclear translocation and DNA repair.
  • TIE2-caveolin-1 interaction and phosphorylation are critical for TIE2's role in DNA repair.
  • Targeting TIE2 and caveolin-1 concurrently offers a promising strategy for glioblastoma radiosensitization.
Keywords:
TIE2brain tumorcaveolin-1nuclear translocationnuclear transportradioresistanceradiosensitivity

More Related Videos

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins11:25

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins

Published on: October 4, 2017

7.2K
Heterokaryon Technique for Analysis of Cell Type-specific Localization09:31

Heterokaryon Technique for Analysis of Cell Type-specific Localization

Published on: March 11, 2011

17.0K

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.9K
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...
3.2K
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
3.3K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
6.5K
Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
9.7K