Researchers find new way to control genes often involved in cancer growth

July 8, 2016, H. Lee Moffitt Cancer Center & Research Institute
cancer
Killer T cells surround a cancer cell. Credit: NIH

Cancer is a group of more than 100 different diseases. All are driven by cells and genes that escape the normal process of division and begin their own plan to replicate in the body. Advances in genetics and molecular biology are providing researchers with better knowledge of the genetic mutations and cell alterations that can lead to cancer, and also how to utilize that information to develop preventive measures and therapies to target the diseases.

Moffitt Cancer Center, a leader in molecular cancer research, and a research team led by Jia Fang, Ph.D., assistant member of the Tumor Biology Department, has discovered a new way to control the activity of SETDB1, a that is often upregulated in cancer. Their findings have been published in the June 16 issue of Molecular Cell.

The novel mechanism to control the protein function is called monoubiquitination. Proteins can be regulated by a process called ubiquitination, in which an ubiquitin molecule is added to a protein. Ubiquitin modification can result in a number of different effects. The addition of many ubiquitin molecules can target a protein for degradation, while the addition of a single ubiquitin molecule (monoubiquitination) can lead to activation of protein signaling pathways or target other proteins for ubiquitination. Ubiquitin is usually added to a protein through an ordered series of events - activation by an E1 , conjugation by an E2 enzyme and ligation by an E3 enzyme.

SETDB1 regulates the level of DNA compaction and gene expression. When SETDB1 is active, the expression levels of target genes are repressed. Given its critical role in controlling gene expression, SETDB1 must be precisely regulated to ensure that molecular processes run properly.

Moffitt researchers performed molecular studies to show for the first time that SETDB1 is constitutively modified by a single ubiquitin molecule. The ubiquitination event is mediated directly by E1 and E2 enzymes, without the traditional involvement of an E3 enzyme. Importantly, this monoubiquitination serves as an integral part of SETDB1 to render its activity and leads to inhibition of target .

"This is the first demonstration that a constitutive monoubiquitination by an E2 enzyme complements the function of a key enzyme. These results suggest that this class of E2 enzymes is an attractive target for therapeutics," said Fang.

Explore further: Research explains the role of the gene BRCA1 in DNA repair

More information: Lidong Sun et al, E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1, Molecular Cell (2016). DOI: 10.1016/j.molcel.2016.04.022

Related Stories

Research explains the role of the gene BRCA1 in DNA repair

May 30, 2016
Scientists at the University of Birmingham are a step closer to understanding the role of the gene BRCA1. Changes in this gene are associated with a high risk of developing breast and ovarian cancer.

A single enzyme with the power of three could offer shortcut to therapeutic target

April 19, 2016
Researchers identified a single enzyme doing the work of a trio thought necessary to control a common cellular signaling process being pursued as a therapeutic target.

New mechanism for cancer progression discovered

November 27, 2012
The protein Ras plays an important role in cellular growth control. Researchers have focused on the protein because mutations in its gene are found in more than 30 percent of all cancers, making it the most prevalent human ...

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.