Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

5.7K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
5.7K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

5.5K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
5.5K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.0K
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...
5.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.3K
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...
3.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

FOXC2 represses NFAT1-dependent transcription through a DNA-facilitated protein-protein interaction.

Nucleic acids research·2026
Same author

Molecular mechanisms underlying HRK interaction with BCL-XL and BCL-2 reveal specificity determinants for BH3 mimetics.

iScience·2025
Same author

Deciphering molecular specificity in MCL-1/BAK interaction and its implications for designing potent MCL-1 inhibitors.

Cell death and differentiation·2025
Same author

Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer.

Communications biology·2025
Same author

Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4.

European journal of medicinal chemistry·2024
Same author

Structural characterization of the DNA binding mechanism of retinoic acid-related orphan receptor gamma.

Structure (London, England : 1993)·2024
Same journal

GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.

Biochemical and biophysical research communications·2026
Same journal

A miR-382-5p-PORCN axis modulates endogenous Wnt signaling during palatal development.

Biochemical and biophysical research communications·2026
Same journal

Development of a vitamin-related gene signature to predict the immune characteristics and prognosis of glioma.

Biochemical and biophysical research communications·2026
Same journal

Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.

Biochemical and biophysical research communications·2026
Same journal

Necrotic tumor cells contribute to pro-tumoral responses and inflammatory mediator production via NF-κB activation in oral squamous cell carcinoma.

Biochemical and biophysical research communications·2026
Same journal

GPR4 promotes ferroptosis in nucleus pulposus cells via MAPK-dependent mitophagy suppression.

Biochemical and biophysical research communications·2026
See all related articles

Related Experiment Video

Updated: May 16, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

10.8K

Structural analysis of apoptotic MCL1-HRK complex.

Jiaqi Wang1, Longying Jiang2, Hudie Wei1

  • 1Department of Oncology, NHC Key Laboratory of Cancer Proteomics & State Local Joint Engineering Laboratroy for Anticancer Drugs, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Biochemical and Biophysical Research Communications
|May 9, 2025
PubMed
Summary
This summary is machine-generated.

Harakiri (HRK) BH3 peptide binds myeloid cell leukemia 1 (MCL1), an anti-apoptotic protein crucial for cancer cell survival. Understanding this interaction provides insights for developing novel BH3 mimetic cancer therapies.

Keywords:
BCL-2 familyBH3 mimeticsHarakiriMyeloid cell leukemia 1

More Related Videos

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
07:22

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

3.2K
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.1K

Related Experiment Videos

Last Updated: May 16, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

10.8K
Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
07:22

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

3.2K
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.1K

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Cancer Therapeutics

Background:

  • Myeloid cell leukemia 1 (MCL1) is a BCL-2 family anti-apoptotic protein essential for malignant cell survival.
  • Targeting MCL1 with BH3 mimetics is a promising anticancer strategy.
  • Harakiri (HRK) is a pro-apoptotic BH3-only protein.

Purpose of the Study:

  • To biochemically and structurally characterize the interaction between the HRK BH3 peptide and MCL1.
  • To provide insights for the rational design of MCL1-targeting BH3 mimetics.

Main Methods:

  • Biochemical binding assays to determine binding affinity (EC50).
  • X-ray crystallography to resolve the complex structure at 1.4 Å resolution.
  • Structural analysis of protein-ligand interactions.

Main Results:

  • HRK BH3 peptide showed moderate affinity for MCL1 (EC50 = 42.7 nM).
  • The crystal structure revealed the α-helical HRK BH3 peptide binding to the canonical hydrophobic groove of MCL1.
  • Specific residue interactions (leucine, threonine, K38, D42) with MCL1 were identified, including electrostatic and hydrogen bonding.

Conclusions:

  • The study elucidates the molecular basis of HRK BH3 peptide binding to MCL1.
  • Detailed structural insights advance the understanding of MCL1's anti-apoptotic function.
  • Findings offer a foundation for optimizing BH3 mimetics for cancer therapy.