CSIG inhibits PTEN translation in replicative senescence
Liwei Ma1, Na Chang, Shuzhen Guo
1Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
Molecular and Cellular Biology
|August 6, 2008
Summary
Cellular senescence-inhibited gene protein (CSIG) regulates cell proliferation and delays replicative senescence by suppressing PTEN translation. This discovery highlights CSIG as a key factor in cellular aging.
Area of Science:
- Cell Biology
- Molecular Biology
- Aging Research
Background:
- Replicative senescence is a key factor in organismal aging.
- The molecular mechanisms regulating cellular senescence are not fully understood.
Purpose of the Study:
- To identify novel genes involved in regulating cellular senescence.
- To elucidate the role of CSIG (RSL1D1) in cellular senescence and proliferation.
Main Methods:
- Suppresss subtractive hybridization to identify CSIG.
- Gene overexpression and knockdown experiments.
- Western blotting and luciferase reporter assays to study protein expression and regulation.
- Cell proliferation and senescence assays.
Main Results:
- CSIG expression declines with replicative senescence.
- CSIG negatively regulates PTEN and p27(Kip1) expression, promoting cell proliferation.
- CSIG interacts with PTEN mRNA's 5' UTR, suppressing PTEN translation.
- CSIG delays senescence, while CSIG knockdown accelerates it; PTEN is required for CSIG's senescence-regulating effects.
Conclusions:
- CSIG is a novel regulator of replicative senescence.
- CSIG mediates senescence through PTEN regulation via translational suppression.
- CSIG plays a significant role in controlling cellular aging processes.
Related Concept Videos
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...