Related Experiment Video

Updated: Dec 17, 2025

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.3K

Lys05 - A Promising Autophagy Inhibitor in the Radiosensitization Battle: Phosphoproteomic Perspective

Martin Ondrej1, Lucie Cechakova1, Ivo Fabrik2

  • 1Department of Radiobiology, Faculty of Military Health Sciences, University of Defense in Brno, Hradec Kralove, Czech Republic.

Cancer Genomics & Proteomics
|June 25, 2020
PubMed
Abstract

Insights

Lys05 inhibits autophagy, a key factor in radiotherapy resistance. This study reveals Lys05 down-regulates Unc-51 like autophagy-activating kinase 1 (ULK1) phosphorylation, offering insights for lung cancer precision medicine.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Autophagy plays a critical role in radioresistance in cancer.
  • Lys05 demonstrates potential in improving radiotherapy outcomes by inhibiting autophagy.
  • The precise molecular mechanisms of Lys05-mediated autophagy inhibition require elucidation.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying Lys05-induced autophagy inhibition.
  • To investigate the role of phosphoproteomics in understanding autophagy regulation.

Main Methods:

  • Utilized radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative).
  • Employed quantitative phosphoproteomics to identify molecular targets.
  • Analyzed protein regulation during autophagy induction and inhibition.

Main Results:

  • Autophagy was induced early after irradiation and inhibited at later stages.
  • Early autophagy induction involved regulatory proteins Sequestosome-1 (SQSTM1) and proline-rich AKT1 substrate 1 (AKT1S1).
  • Late-stage autophagy inhibition was primarily due to down-regulation of Unc-51 like autophagy-activating kinase 1 (ULK1) via phosphorylation at Ser638.

Conclusions:

  • Phosphoproteomic analysis provides novel insights into autophagy signaling in lung cancer.
  • Understanding Lys05's mechanism can aid in developing targeted cancer therapies.
  • This research supports the advancement of precision medicine for lung cancer treatment.
Keywords:
Lys05Phosphoproteomicsautophagyinhibitorlung cancer

More Related Videos

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry11:39

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

Published on: July 21, 2017

32.0K
siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.6K

Related Concept Videos

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,...
5.5K
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...
4.1K
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...
4.5K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.6K
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...
5.1K