Featured Research

from universities, journals, and other organizations

Upending a cancer dogma: Cyclin D, long believed to promote cancer, actually activates tumor suppressor

Date:
July 2, 2014
Source:
University of California, San Diego Health Sciences
Summary:
A protein essential to regulating cell cycle progression – the process of cell division and replication – activates a key tumor suppressor, rather than inactivating it as previously thought, researchers report. The findings fundamentally change the understanding of G1 cell cycle regulation and the molecular origins of many associated cancers.

Researchers at the University of California, San Diego School of Medicine say a protein essential to regulating cell cycle progression -- the process of cell division and replication -- activates a key tumor suppressor, rather than inactivating it as previously thought.

Related Articles


"The finding is the result of literally 20 years of work in my lab," said Steven F. Dowdy, PhD, professor in the Department of Cellular and Molecular Medicine at UC San Diego. "It completely turns upside-down what was thought to be a fundamental aspect of cell cycle progression in all cancer cells driven by one of the most common genetic pathways mutated in cancer, namely the p16-cyclin D pathway."

The findings are published in the journal eLife.

Cyclin D is synthesized during the first stage of cell replication and is believed to help drive the complex, multi-stage process, including interaction with the retinoblastoma (Rb) protein, whose function is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide. Rb acts as a tumor suppressor.

But mutated or dysfunctional Rb is associated with several major cancers and Cyclin D has long been described as an oncogene that promotes cancer because it was believed to inactivate the Rb tumor suppressor function through a process called phosphorylation, which involves phosphate molecules being added to proteins, essentially turning them on or off.

Dowdy and colleagues painstakingly counted the number of phosphates added to Rb during cell cycle progression. There are as many as 14, but the scientists found that cyclin D adds just a single phosphate at one, and only one, of the 14 locations during the early G1 phase of cell cycle progression, essentially make 14 different versions of the Rb tumor suppressor. The single phosphate serves to activate Rb, not inactivate it as had been thought for over 20 years.

The researchers said the findings fundamentally change the understanding of G1 cell cycle regulation and the molecular origins of many associated cancers. It is critically important to understand how a genetic pathway actually functions and the consequences of interrupting it, especially in this case where there are multiple drug inhibitors of cyclin D being tested in clinical trials for breast cancer.

Moreover, how the next cyclin, cyclin E, that actually does inactivate Rb becomes activated has not been heavily investigated because it was thought to be the less important second domino, whereas we now know it is the first domino, added Dowdy.


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. M. Narasimha, M. Kaulich, G. S. Shapiro, Y. J. Choi, P. Sicinski, S. F. Dowdy. Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. eLife, 2014; 3 (0): e02872 DOI: 10.7554/eLife.02872

Cite This Page:

University of California, San Diego Health Sciences. "Upending a cancer dogma: Cyclin D, long believed to promote cancer, actually activates tumor suppressor." ScienceDaily. ScienceDaily, 2 July 2014. <www.sciencedaily.com/releases/2014/07/140702122242.htm>.
University of California, San Diego Health Sciences. (2014, July 2). Upending a cancer dogma: Cyclin D, long believed to promote cancer, actually activates tumor suppressor. ScienceDaily. Retrieved January 27, 2015 from www.sciencedaily.com/releases/2014/07/140702122242.htm
University of California, San Diego Health Sciences. "Upending a cancer dogma: Cyclin D, long believed to promote cancer, actually activates tumor suppressor." ScienceDaily. www.sciencedaily.com/releases/2014/07/140702122242.htm (accessed January 27, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, January 27, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Disneyland Measles Outbreak Spreads To 5 States

Disneyland Measles Outbreak Spreads To 5 States

Newsy (Jan. 24, 2015) Much of the Disneyland measles outbreak is being blamed on the anti-vaccination movement. The CDC encourages just about everyone get immunized. Video provided by Newsy
Powered by NewsLook.com
Growing Measles Outbreak Worries Calif. Parents

Growing Measles Outbreak Worries Calif. Parents

AP (Jan. 23, 2015) Public health officials are rushing to contain a measles outbreak that has sickened 70 people across 6 states and Mexico. The AP&apos;s Raquel Maria Dillon has more. (Jan. 23) Video provided by AP
Powered by NewsLook.com
Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins