Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL
GLOBETECH PUBLISHING LLC

A Pair of Gene Splice Isoforms Has Opposite Effects on Cancer Development

By BiotechDaily International staff writers
Posted on 21 Apr 2014
Two distinct splice isoforms of the MAP kinase interacting serine/threonine kinase 2 (MKNK2) gene have dramatically different roles in cancer development and growth.

It is known that the protein products of MKNK2 phosphorylate the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation, and malignant cell proliferation. However, it has come to light that MKNK2 is alternatively spliced with the two splicing isoforms having different last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it.

Investigators at the Hebrew University of Jerusalem (Israel) reported in the April 10, 2014, online edition of the journal Cell Reports that the Mnk2a isoform was a tumor suppressor that was downregulated in human cancers. This isoform interacted with, phosphorylated, and activated p38-MAPK, leading to activation of its target genes and to p38alpha-mediated cell death. Thus, Mnk2a downregulation by alternative splicing was a tumor suppressor mechanism that was lost in some breast, lung, and colon tumors.

On the other hand, the Mnk2b isoform was found to be pro-oncogenic and did not activate p38-MAPK, while still enhancing eIF4E phosphorylation.

These results suggested that Mnk2 alternative splicing served as a switch in several cancers to downregulate a tumor suppressor isoform (Mnk2a) that activates the p38-MAPK stress pathway and to induce an isoform (Mnk2b) that does not activate this pathway and is pro-oncogenic.

"The mechanism we discovered explains how cancer cells eliminate the anticancer form of Mnk2 without changing their DNA, and how they become resistant to anticancer treatments—a problem which exists for almost every cancer treatment today," said senior author Dr. Rotem Karni, senior lecturer of biochemistry and molecular biology at the Hebrew University of Jerusalem.

Related Links:

Hebrew University of Jerusalem 




Channels

Drug Discovery

view channel
Image: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.