Related Experiment Video

Updated: Jan 23, 2026

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.5K

Blocking transmembrane219 protein signaling inhibits autophagy and restores normal cell death

Sean Joyce1, Adel M Nour1

  • 1Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, United States of America.

Plos One
|June 21, 2019
PubMed

Insights

Researchers discovered Transmembrane 219 (TM219) protein activates autophagy, crucial for tumor cell survival. They developed a novel peptide (SCTT-pHLIP) to inhibit TM219, offering a new strategy for cancer therapy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Autophagy is critical for tumor therapy and dormant tumor cell survival.
  • Transmembrane 219 (TM219) is a small membrane protein expressed in most human tissues.
  • The role of TM219 in autophagy regulation was previously unknown.

Purpose of the Study:

  • To elucidate the novel function of TM219 as an autophagy activator.
  • To identify TM219 interacting partners, specifically calmodulin and calmodulin-dependent protein kinase II.
  • To develop and test a peptide-based inhibitor of TM219 for potential cancer therapy.

Main Methods:

  • Biochemical approaches to identify TM219 protein complex components.
  • In vitro reconstitution and fluorescence anisotropy to study TM219-calmodulin interactions.
  • Development of a synthetic peptide (SCTT) conjugated to pHLIP for cellular delivery and testing in triple-negative breast cancer cells.

Main Results:

  • TM219 was identified as an autophagy activator.
  • Calmodulin and calmodulin-dependent protein kinase II were found to be part of the TM219 protein complex.
  • The SCTT-pHLIP peptide effectively inhibited TM219 function in triple-negative human breast cancer cells in 3D culture.

Conclusions:

  • TM219 possesses a novel function as an autophagy activator.
  • A synthetic peptide-based approach (SCTT-pHLIP) provides an efficient strategy to inhibit TM219.
  • This discovery opens new avenues for targeting autophagy in cancer therapy.

More Related Videos

Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond09:00

Live Cell Imaging of Early Autophagy Events: Omegasomes and Beyond

Published on: July 27, 2013

19.2K
Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells15:53

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Published on: August 21, 2013

15.5K

Related Concept Videos

Restorative Care01:19

Restorative Care

Restorative care is provided once a patient has been discharged from a healthcare facility and requires additional services. The additional services include home care, rehabilitation programs, and extended care. Restorative care centers help the patient regain their previous level of functioning or acquire a new level of functioning due to the incapacitating effects of a disease or a disability. It aims to assist patients in enhancing their quality of life by encouraging independence,...
2.4K
What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
129.9K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
9.6K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.4K
Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
54.0K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.7K