Related Experiment Video

Updated: Feb 6, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

3.5K

Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism

Shivangi Agarwal1, Kyle Paul Smith1, Yizhuo Zhou2

  • 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

The Journal of Cell Biology
|August 30, 2018
PubMed

Insights

Cdt1 binds microtubules and localizes to kinetochores, impacting chromosome segregation. Aurora B phosphorylation of Cdt1 disrupts this interaction, affecting kinetochore-microtubule attachments during mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Robust kinetochore-microtubule (kMT) attachment is essential for accurate chromosome segregation during cell division.
  • Cdt1 is known for its role in DNA replication origin licensing but also localizes to kinetochores during mitosis.

Purpose of the Study:

  • To investigate the novel mitotic role of Cdt1 beyond DNA replication.
  • To elucidate the mechanism by which Cdt1 influences kMT attachments and chromosome segregation.

Main Methods:

  • Depletion of Cdt1 in G2/M phase cells.
  • Analysis of kMT attachments and mitotic progression.
  • In vitro binding assays to assess Cdt1-microtubule interactions.
  • Deletion mapping of Cdt1 to identify MT-binding domains.
  • Investigation of Aurora B kinase interaction and phosphorylation of Cdt1.

Main Results:

  • Cdt1 directly binds to microtubules (MTs) and localizes to mitotic spindle MTs and kinetochores.
  • Specific domains of Cdt1 (middle and C-terminal winged-helix) are crucial for MT binding.
  • Aurora B kinase interacts with and phosphorylates Cdt1.
  • Phosphorylation of Cdt1 by Aurora B reduces its MT binding affinity, leading to defective kMT attachments and delayed mitosis.

Conclusions:

  • Cdt1 plays a direct, independent role in mitosis by binding to MTs.
  • Aurora B-mediated phosphorylation of Cdt1 is a key regulatory mechanism controlling kMT stability.
  • This phosphorylation-dependent regulation of Cdt1's MT-binding activity likely contributes to the fidelity of chromosome segregation.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

19.4K
Development of a Microfluidics-Based Approach for Investigating Microtubule Polymer Mechanics06:03

Development of a Microfluidics-Based Approach for Investigating Microtubule Polymer Mechanics

Published on: May 30, 2025

839

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.8K
Microtubules01:35

Microtubules

There are three types of cytoskeletal structures in eukaryotic cells—microfilaments, intermediate filaments, and microtubules. With a diameter of about 25 nm, microtubules are the thickest of these fibers. Microtubules carry out a variety of functions that include cell structure and support, transport of organelles, cell motility (movement), and the separation of chromosomes during cell division.
99.7K
Microtubules01:18

Microtubules

Microtubules are the thickest cytoskeletal filaments with a diameter of 25 nm. In prokaryotic organisms, microtubules are commonly found in locomotory appendages like cilia and flagella. In eukaryotic cells, microtubules form specialized extensions for moving fluid over the surface, like those found in cells lining the intestine.
Microtubules have two structurally similar globular protein subunits: α and β tubulins. In the cytosol, the α and β tubulins form a heterodimer....
10.7K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.5K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Attachment01:20

Attachment

Attachment is vital for infant development, as warm social interactions support growth and well-being. In a classic 1958 study by Harry Harlow, the significance of warmth and comfort in forming attachments was examined. Harlow separated newborn monkeys from their mothers and provided two artificial "mothers": one made of cold wire and the other covered in soft cloth. Despite the wire mother offering food, the infant monkeys preferred the comfort of the cloth mother, demonstrating that...
528