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

Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...

You might also read

Related Articles

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

Sort by
Same author

Accuracy of data routinely collected by Australian hospitals for identifying infective endocarditis, causative organisms and clinical outcomes: a diagnostic accuracy study.

Internal medicine journal·2026
Same author

A novel screening tool is effective in the early detection of peripheral nerve injury with elbow and forearm trauma subjects: A case series.

Journal of hand therapy : official journal of the American Society of Hand Therapists·2026
Same author

"There is never any rest, never enough time and too much to do": a qualitative study of GP work intensity in an Irish context.

BMC primary care·2026
Same author

Teaching for Truth: A Descriptive Qualitative Study of a Classroom Strategy for Teaching Health Students to Recognise the Weight of Colonisation in First Nations Health.

Creative nursing·2026
Same author

Evidence-based intervention to prevent professional burnout in resident oncology doctors in a tertiary UK centre: a pilot study.

BMJ supportive & palliative care·2026
Same author

Collaborating to create re-usable training materials to increase knowledge and library professionals' understanding of artificial intelligence.

Health information and libraries journal·2025

Related Experiment Video

Updated: May 27, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

TIN2 stability is regulated by the E3 ligase Siah2.

Monica Bhanot1, Susan Smith

  • 1Molecular Pathogenesis Program and Department of Pathology, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York, USA.

Molecular and Cellular Biology
|November 9, 2011
PubMed
Summary

The E3 ligase Siah2 regulates TIN2 stability, a key component of the shelterin complex. Siah2 targets TIN2 for ubiquitylation and degradation, impacting telomere maintenance and shelterin complex dynamics.

More Related Videos

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity
09:21

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity

Published on: October 22, 2018

Related Experiment Videos

Last Updated: May 27, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity
09:21

Saccharomyces cerevisiae Metabolic Labeling with 4-thiouracil and the Quantification of Newly Synthesized mRNA As a Proxy for RNA Polymerase II Activity

Published on: October 22, 2018

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Telomeres protect chromosome ends and are regulated by the shelterin complex.
  • TIN2 is a central subunit of shelterin, crucial for its stability and function.
  • Regulation of TIN2 stability is essential for proper telomere maintenance.

Purpose of the Study:

  • To investigate the role of the E3 ligase Siah2 in regulating TIN2 stability.
  • To elucidate the mechanism by which Siah2 affects TIN2 protein levels and telomere localization.
  • To understand the consequences of Siah2-mediated TIN2 regulation on other shelterin subunits.

Main Methods:

  • In vivo ubiquitylation assays to detect TIN2 modification by Siah2.
  • In vitro ubiquitylation assays using purified proteins to confirm Siah2's ligase activity on TIN2.
  • Siah2 depletion and overexpression studies in human cells to assess TIN2 stability and telomere localization.
  • Analysis of other shelterin subunits (TRF1, TRF2, TPP1) localization upon Siah2-mediated TIN2 depletion.

Main Results:

  • TIN2 directly binds to and is ubiquitylated by Siah2 in vivo and in vitro.
  • Siah2 depletion stabilizes TIN2 protein, while Siah2 overexpression leads to TIN2 loss at telomeres.
  • Siah2-mediated TIN2 depletion results in TRF1 and TRF2 remaining at telomeres, unlike RNAi-mediated TIN2 depletion.
  • TPP1 is lost from telomeres following Siah2-mediated TIN2 depletion, despite unchanged protein levels.

Conclusions:

  • Siah2 acts as an E3 ligase that regulates TIN2 protein stability and telomere localization.
  • Post-translational regulation of TIN2 by Siah2 influences the dynamics of the shelterin complex.
  • Siah2-mediated TIN2 removal may facilitate dynamic remodeling of shelterin and associated factors during the cell cycle.