Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
BioConferenceLive

Decisive Role in Cell Division Identified for Centrosomal Protein

By BiotechDaily International staff writers
Posted on 30 Aug 2012
Image: The mitotic spindle (microtubules in red, DNA in blue) and the centrosomes (in yellow). (Photo courtesy of Dr. S. Sdelci, IRB Barcelona).
Image: The mitotic spindle (microtubules in red, DNA in blue) and the centrosomes (in yellow). (Photo courtesy of Dr. S. Sdelci, IRB Barcelona).
Image: Depicted are four cells (DNA in blue and a centrosomal protein in red). The cell on the left is in mitosis - observe how the DNA condenses in the chromosomes and the two centrosomes separate and accumulate proteins (maturation) (Photo courtesy of Dr. S. Sdelci, IRB Barcelona).
Image: Depicted are four cells (DNA in blue and a centrosomal protein in red). The cell on the left is in mitosis - observe how the DNA condenses in the chromosomes and the two centrosomes separate and accumulate proteins (maturation) (Photo courtesy of Dr. S. Sdelci, IRB Barcelona).
The answer to an elusive question about signaling in chromosome distribution and separation has been provided by the discovery of a key role for a centrosomal protein kinase. The kinase also has potential importance as a new candidate among cell division factors being targeted in the development of drug treatments for cancer.

The study, headed by principal researchers Joan Roig, PhD, at the Institute for Research in Biomedicine (IRB Barcelona; Barcelona, Spain) and Isabelle Vernos, PhD, at the Center for Genomic Regulation (CRG; Barcelona, Spain) highlights the protein kinase Nek9 as an essential and decisive factor in a pathway involved in ensuring efficient and accurate movement of chromosomes during cell division. γ-tubulin recruitment to and accumulation at the centrosome during the centrosome maturation stage of mitosis is known to depend on the adaptor protein NEDD1/GCP-WD and to be controlled by the kinase Plk1. Surprisingly, and although Plk1 binds and phosphorylates NEDD1 at multiple sites, the mechanism by which this kinase promotes centrosomal recruitment of γ-tubulin has remained elusive. Using Xenopus egg extracts and mammalian cells, the scientists found that Nek9, a kinase required for normal mitotic progression and spindle organization, phosphorylates NEDD1, driving its recruitment and thereby that of γ-tubulin to the centrosome. This role of Nek9 requires its activation by Plk1-dependent phosphorylation.


Errors in chromosome distribution cause many spontaneous miscarriages, some genetic defects such as trisomies, and are related to the development of tumors. Nek9 exerts its action between two molecules, Plk1 and Eg5, of interest as antitumoral agents and for which inhibitors are already in advanced stages of clinical trials. Nek9 could well be added to the list of cell division target candidates. “Through this study we demonstrate that a fourth family of proteins, namely NIMA and specifically Nek9, exert functions in cell division as important as those undertaken by the widely studied CDK (cdk1), Polo (Plk1) and Aurora (Aurora A and B) kinases”, explains Dr. Roig. “Without Nek9 the spindle would not form properly and cell division would be hindered, the cells would die or cause aneuploidies, with unequal distribution of chromosomes, an event that is common in tumors,” explains Dr. Vernos. The pharmaceutical industry is currently testing new drugs that inhibit Plk1, Eg5, and Aurora. “We are doing double-edged work: we describe how proteins involved in the initial stages of cell division are related in time and space, and in parallel we highlight the possible therapeutic tools, whether markers of disease or antimitotic agents, that can stop division and tumor growth”, says Dr. Roig.

The findings were published July 19, 2012, in the journal Current Biology.

Related Links:

Institute for Research in Biomedicine, Barcelona
Center for Genomic Regulation




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Blocking the activity of HSP101 may imprison the malaria parasite inside its protective vacuole within the red blood cell. In the electron micrograph, the malaria parasites appear in blue and uninfected red blood cells are shown in red (Photo courtesy of the [US] National Institute of Allergy and Infectious Diseases).

Heat Shock Protein Plays Critical Role in Malaria Parasite Protein Trafficking

A pair of recent papers described the molecular operators that enable the malaria parasite Plasmodium falciparum to export a large variety of proteins across the parasitophorous vacuolar membrane (PVM)... Read more

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel
Image: A one-year-old baby sits in a brain scanner, called magnetoencephalography (MEG)—a noninvasive approach to measuring brain activity. The baby listens to speech sounds such as “da” and “ta” played over headphones while researchers record her brain responses (Photo courtesy of the Institute for Learning & Brain Sciences at the University of Washington).

Brain Scanner Shows Infants’ Brains Rehearse Speech Sounds Months Before Their First Words

New research in 7- and 11-month-old infants revealed that speech sounds stimulate brain regions that coordinate and plan motor movements for speech. The new study suggests that babies’ brains begin establishing... Read more

Business

view channel

Cancer Immunotherapy Sector Predicted to Surge to USD 9 Billion Across Major Pharma Through 2022

The immunotherapy market will experience substantial growth through 2022, increasing from USD 1.1 billion in 2012 to nearly USD 9 billion in 2022 (corresponding to 23.8% annual growth) in the United Kingdom, United States, France, Germany, Italy, Spain, and Japan, according to recent market research. This notable growth... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.