Related Experiment Video

Updated: May 5, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.3K

RABL6A, a novel RAB-like protein, controls centrosome amplification and chromosome instability in primary fibroblasts

Xuefeng Zhang1, Jussara Hagen, Viviane P Muniz

  • 1Department of Pharmacology, University of Iowa, Iowa City, Iowa, United States of America.

Plos One
|November 28, 2013
PubMed

Insights

RABL6A protein prevents cell division errors like centrosome amplification, aneuploidy, and multinucleation. This discovery reveals a new role for RABL6A in maintaining genomic stability, independent of ARF and p53.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • RABL6A (RAB-like 6 isoform A) is a novel protein linked to the Alternative Reading Frame (ARF) tumor suppressor.
  • ARF functions in cancer prevention via p53-dependent and independent pathways.
  • The specific functions and cellular roles of RABL6A remain largely uncharacterized.

Purpose of the Study:

  • To investigate the biological consequences of RABL6A silencing in mouse embryo fibroblasts (MEFs).
  • To determine the dependence of RABL6A function on ARF and p53.
  • To elucidate the mechanism by which RABL6A influences cell cycle regulation and genomic stability.

Main Methods:

  • Silencing of RABL6A in primary MEFs with varying ARF and p53 expression.
  • Assessment of centrosome number, ploidy, and nuclear status.
  • Analysis of nucleophosmin (NPM) phosphorylation at threonine-199 and Cdk2 activity.

Main Results:

  • RABL6A depletion led to centrosome amplification, aneuploidy, and multinucleation in MEFs, irrespective of ARF and p53.
  • Centrosome amplification in RABL6A-depleted p53-/- MEFs was due to reduplication mediated by Cdk2-dependent NPM hyperphosphorylation (NPM-T199).
  • RABL6A acts independently of ARF and p53 to restrict NPM-T199 phosphorylation.

Conclusions:

  • RABL6A plays a critical role in regulating centrosome duplication and maintaining chromosome stability.
  • The findings highlight an ARF/p53-independent mechanism for RABL6A in preventing genomic instability.
  • RABL6A is essential for ensuring genomic integrity in non-transformed cells, potentially impacting cancer prevention.

More Related Videos

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes09:39

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes

Published on: December 20, 2014

14.8K
Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins05:35

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

15.1K

Related Concept Videos

Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
5.7K
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.9K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.4K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
3.7K
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.
32.1K