Featured Research

from universities, journals, and other organizations

Enzyme For Ubiquitin-dependent Protein Degradation Linked To Cellular Senescence

Date:
May 22, 2008
Source:
Cell Press
Summary:
A new study identifies a pivotal role for the CUL7 E3 ubiquitin ligase in growth control. The research makes an exciting new connection between the regulation of protein degradation and the initiation of cellular senescence.

A new study, published by Cell Press in the May 23rd issue of the journal Molecular Cell, identifies a pivotal role for the CUL7 E3 ubiquitin ligase in growth control. The research makes an exciting new connection between the regulation of protein degradation and the initiation of cellular senescence.

Related Articles


CUL7 E3 is an E3 ubiquitin ligase that plays a critical role in mediating selective degradation of target proteins and, therefore, has a substantial impact on numerous biological processes. Recent genetic research has linked the absence of CUL7 with growth retardation. Dr. Zhen-Qiang Pan from The Mount Sinai School of Medicine and colleagues designed a series of studies to further investigate mechanisms that underlie CUL7-mediated growth regulation.

The researchers found that the CUL7 E3 ligase targeted the insulin receptor substrate 1 (IRS-1) for ubiquitin-mediated degradation and that, conversely, IRS-1 accumulated in CUL7-deficient cells. IRS-1 is a key mediator of the insulin/insulin-like growth factor 1-signaling system and plays a critical role in organismal growth and aging. Further, CUL7-mediated IRS-1 degradation required activity of mammalian target of rapamycin (mTOR), a master regulator of cell growth.

Interestingly, CUL7-deficient cells exhibited multiple biochemical and morphological characteristics associated with senescent cells, specifically with oncogene-induced senescence. Oncogene-induced senescence is an antiproliferative program that is initiated by tumor suppressors in response to oncogenic activation of hyperproliferation.

"Our working hypothesis is that aberrant accumulation of IRS-1, resulting from inactivation of the CUL7 E3, is an oncogenic stimulus that triggers cellular senescence, presumably through sustained MAPK activation and/or increased Akt signaling, both of which were previously shown to induce senescence," explains Dr. Pan. "These results also raise the possibility that senescence contributes to the pathogenesis of growth retardation observed in patients with disorders linked to CUL7 mutations, such as Yakuts dwarfism syndromes and the 3-M syndrome."

The researchers include Xinsong Xu, The Mount Sinai School of Medicine, New York, NY; Antonio Sarikas, The Mount Sinai School of Medicine, New York, NY; Dora C. Dias-Santagata, The Mount Sinai School of Medicine, New York, NY; Georgia Dolios, The Mount Sinai School of Medicine, New York, NY; Pascal J. Lafontant, Indiana University School of Medicine, Indianapolis, IN; Shih-Chong Tsai, Indiana University School of Medicine, Indianapolis, IN; Wuqiang Zhu, Indiana University School of Medicine, Indianapolis, IN; Hidehiro Nakajima, Indiana University School of Medicine, Indianapolis, IN; Hisako O. Nakajima, Indiana University School of Medicine, Indianapolis, IN; Loren J. Field, Indiana University School of Medicine, Indianapolis, IN; Rong Wang, The Mount Sinai School of Medicine, New York, NY; and Zhen-Qiang Pan, The Mount Sinai School of Medicine, New York, NY.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Enzyme For Ubiquitin-dependent Protein Degradation Linked To Cellular Senescence." ScienceDaily. ScienceDaily, 22 May 2008. <www.sciencedaily.com/releases/2008/05/080522120604.htm>.
Cell Press. (2008, May 22). Enzyme For Ubiquitin-dependent Protein Degradation Linked To Cellular Senescence. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2008/05/080522120604.htm
Cell Press. "Enzyme For Ubiquitin-dependent Protein Degradation Linked To Cellular Senescence." ScienceDaily. www.sciencedaily.com/releases/2008/05/080522120604.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
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