Related Experiment Video

Updated: Sep 29, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress

Seiji Inoshita1, Kohsuke Takeda, Takiko Hatai

  • 1Laboratory of Cell Signaling, Department of Hard Tissue Engineering, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

The Journal of Biological Chemistry
|September 12, 2002
PubMed

Insights

Oxidative stress triggers JNK activation, leading to cell death. This study reveals JNK inactivates the anti-apoptotic protein Mcl-1 (myeloid cell leukemia 1) via phosphorylation, promoting oxidative stress-induced apoptosis.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress is a known inducer of apoptosis (programmed cell death) via JNK (c-Jun N-terminal kinase) activation and subsequent caspase cascades.
  • The precise mechanisms by which JNK influences mitochondrial function and apoptosis remain incompletely understood.
  • Myeloid cell leukemia 1 (Mcl-1) is a critical anti-apoptotic protein belonging to the Bcl-2 family, playing a key role in cell survival.

Purpose of the Study:

  • To investigate the role of Mcl-1 phosphorylation in oxidative stress-induced apoptosis.
  • To elucidate the specific sites and mechanism of JNK-mediated Mcl-1 regulation under oxidative stress conditions.

Main Methods:

  • Utilized hydrogen peroxide (H2O2) to induce oxidative stress in cellular models.
  • Employed techniques to assess JNK activation and its effect on Mcl-1 phosphorylation.
  • Generated and tested cells expressing unphosphorylatable Mcl-1 mutants to evaluate anti-apoptotic function.

Main Results:

  • Demonstrated that JNK phosphorylates Mcl-1 at specific residues (Ser-121 and Thr-163) upon H2O2 stimulation.
  • Showed that cells expressing Mcl-1 variants resistant to phosphorylation exhibited enhanced anti-apoptotic activity under oxidative stress.
  • Indicated that JNK-dependent phosphorylation leads to Mcl-1 inactivation.

Conclusions:

  • JNK-mediated phosphorylation and subsequent inactivation of Mcl-1 is a significant mechanism contributing to oxidative stress-induced apoptosis.
  • Targeting Mcl-1 phosphorylation could represent a therapeutic strategy to mitigate oxidative stress-related cellular damage.

More Related Videos

Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia09:44

Flow Cytometric Analysis of Mitochondrial Reactive Oxygen Species in Murine Hematopoietic Stem and Progenitor Cells and MLL-AF9 Driven Leukemia

Published on: September 5, 2019

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation09:09

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation

Published on: November 10, 2017

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...