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.”
Source: Cell Press
Related stories:
'Single-Crystal' Superconductors are a Big Step for the Field
(PhysOrg.com) -- In key advances for the field of superconductivity, a research group has created versions of a class of widely studied superconducting compounds that are each one continuous crystal, rather than composed of many crystalline grains. These single-crystal materials are important achievements because they display better properties than polycrystalline types and are easier to study.
Futuristic fridges invade Berlin consumer electronics show
The Ifa, Europe's top consumer electronics show, is normally all about gadgets that make life more entertaining with the latest flat screen televisions, stereo equipment and the like.
Antidepressants need new nerve cells to be effective
Researchers at UT Southwestern Medical Center have discovered in mice that the brain must create new nerve cells for either exercise or antidepressants to reduce depression-like behavior. In addition, the researchers found that antidepressants and exercise use the same biochemical pathway to exert their effects.
Low levels of brain chemical may lead to obesity
A brain chemical that plays a role in long term memory also appears to be involved in regulating how much people eat and their likelihood of becoming obese, according to a National Institutes of Health study of a rare genetic condition.
TiVo shows another profit, but outlook weak
(AP) -- TiVo Inc. posted a quarterly profit for only the third time in its 11-year history Wednesday as the pioneer in digital video recorders boosted margins on hardware and reduced marketing costs in its fiscal second quarter.
Samsung Introduces High-performance, Low-density, SATA II SSDs
Samsung Electronics announced today that it has begun sampling low-density, higher-performance solid state drives (SSDs) that are only 30 percent of the size of 2.5-inch SSDs and highly cost-efficient to manufacture. With the introduction of these smaller, low-capacity SSDs, Samsung now offers an attractive replacement for existing hard drives used in low-cost PCs. Available in densities of 8GB, 16GB and 32GB, the new multi-level-cell SSDs will be mass produced beginning next month.
Study outcome won't sway company on eye drug
(AP) -- What does a company do when there's anecdotal evidence that two of its drugs are equally effective in treating a leading cause of blindness in the elderly, one costing patients $60 per treatment and the other $2,000? In the case of Genentech Inc., nothing.
Why is Greenland covered in ice?
There have been many reports in the media about the effects of global warming on the Greenland ice-sheet, but there is still great uncertainty as to why there is an ice-sheet there at all.