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

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...
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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.

You might also read

Related Articles

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

Sort by
Same author

Targeting the αvβ5 Integrin Modifies the TGF-β-Rich Tumor Microenvironment of Pancreatic Cancer.

Cancer research·2026
Same author

Characterisation of Lates calcarifer primary myoblast proliferation and differentiation from direct cell isolation.

In vitro cellular & developmental biology. Animal·2026
Same author

[Corrigendum] PRIMA‑1 inhibits growth of breast cancer cells by re‑activating mutant p53 protein.

International journal of oncology·2026
Same author

BIT1 as an Effector of EGFR-TKI-induced Apoptosis <i>via</i> TLE1 Inhibition in Lung Adenocarcinoma Cells.

Anticancer research·2026
Same author

Molecular characterization of the A52 murine hepatocellular carcinoma cell line.

Animal models and experimental medicine·2026
Same author

Transcriptomic Characterization of North Queensland Hepatocellular Carcinoma.

Oncology·2025

Related Experiment Video

Updated: Jul 8, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

Anoikis effector Bit1 negatively regulates Erk activity.

Rania Kairouz-Wahbe1, Hector Biliran, Xiuquan Luo

  • 1Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 26, 2008
PubMed
Summary

Bcl-2 inhibitor of transcription (Bit1) protein release triggers apoptosis, but integrin attachment prevents it. Loss of Bit1 in mice causes developmental issues and increased Erk activation, impacting anoikis resistance.

More Related Videos

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/&#945;
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Related Experiment Videos

Last Updated: Jul 8, 2026

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/&#945;
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline
08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Bcl-2 inhibitor of transcription (Bit1) is a mitochondrial protein with peptidyl-tRNA hydrolase activity.
  • Cytoplasmic release of Bit1 induces apoptosis, a process counteracted by integrin-mediated cell attachment.
  • The physiological role and regulatory pathways of Bit1 remain incompletely understood.

Purpose of the Study:

  • To investigate the physiological significance of Bit1 using a conditional knockout mouse model.
  • To elucidate the signaling pathway through which Bit1 regulates apoptosis and anoikis.
  • To determine the role of Erk signaling in Bit1-mediated anoikis resistance.

Main Methods:

  • Generation of a conditional knockout mouse for the Bit1 gene using the Cre-LoxP system.
  • Analysis of Bit1-null mice for developmental phenotypes and survival rates.
  • Assessment of anoikis resistance in mouse embryo fibroblasts (MEFs) from Bit1-null and wild-type littermates.
  • Evaluation of Erk phosphorylation and phosphatase activity in Bit1-deficient cells and tissues.
  • Manipulation of Bit1 and Erk expression in cultured cells to study their interplay.

Main Results:

  • Bit1-null mice exhibited developmental abnormalities, runting syndrome, and early postnatal lethality.
  • MEFs from Bit1-null embryos showed increased resistance to anoikis compared to controls.
  • Bit1 deficiency led to elevated Erk phosphorylation and decreased Erk phosphatase activity.
  • Partial knockdown of Erk reversed the enhanced anoikis resistance observed in Bit1 knockdown cells.

Conclusions:

  • Bit1 plays a critical physiological role in development and survival.
  • A novel Bit1 signaling pathway involving Erk activation regulates anoikis resistance.
  • Bit1 influences Erk signaling by modulating Erk phosphatase activity, highlighting its importance in cellular stress responses.