PTEN prevents tumor cells from growing uncontrollably, and mutations
in the gene encoding this protein are commonly found in many different
types of cancer.
Researchers at Cold Spring Harbor Laboratory in New York have
discovered that a protein called Importin-11 protects the anti-cancer
protein PTEN from destruction by transporting it into the cell nucleus.
PTEN, the Tumor Suppressor protein, Puts a Break on Autoimmune Diseases
The tumor suppressor protein PTEN is essential for proper functioning of regulatory T cells, has a role in autoimmune diseases.
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‘A protein called Importin-11 protects the anti-cancer protein PTEN from destruction by transporting it into the cell nucleus.’
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The study, "The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein," which will be published online February 13 in The Journal of Cell Biology, suggests that the loss of Importin-11 may destabilize PTEN, leading to the development of lung, prostate, and other cancers.
Some patients, however, show low levels of the PTEN
protein even though their PTEN genes are normal. Lloyd Trotman, Muhan
Chen, Dawid Nowak, and colleagues discovered that this may be due to
defects in a protein called Importin-11 that transports PTEN into the
nucleus, sheltering PTEN from cytoplasmic proteins that would otherwise
target it for degradation.
![Understanding How Tumor Suppressor Protein]( "Understanding How Tumor Suppressor Protein")
Pten (short for phosphatase and tensin homolog) safeguards against tumor formation by keeping chromosome numbers intact when a cell splits into two daughter cells.
Several cytoplasmic proteins - NEDD4-1, NDFIP1, and UBE2E1 - combine to tag PTEN with the small molecule ubiquitin. PTEN tagged with multiple ubiquitin molecules can then be recognized and destroyed by the cell's protein degradation machinery. Trotman and colleagues found that Importin-11 protects PTEN from degradation by escorting not only PTEN but also UBE2E1 into the nucleus, thereby breaking up the cytoplasmic ubiquitination apparatus.
Mice lacking Importin-11 showed lower levels of PTEN protein and developed lung adenocarcinomas and prostate neoplasias. Mutations in the gene encoding Importin-11 have been identified in human cancers, and Trotman and colleagues found that tumors from lung cancer patients lacking Importin-11 tended to show low PTEN levels as well. The researchers estimate that loss of Importin-11 may account for the loss of PTEN in approximately one third of lung cancer patients lacking this key anti-cancer protein.
In prostate cancer, loss of Importin-11 predicted disease relapse and metastasis in patients who had had their prostates removed. "We think that the degradation of PTEN after loss or impairment of Importin-11 is a very effective driver of human prostate cancer," says Trotman. "Our results suggest that Importin-11 is the "Achilles' heel" of the ubiquitination system that maintains the correct levels of PTEN inside cells."
Source: Eurekalert
Understanding How Tumor Suppressor Protein 'Pten' Safeguards Against Tumor Formation
Pten (short for phosphatase and tensin homolog) safeguards against tumor formation by keeping chromosome numbers intact when a cell splits into two daughter cells.
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Several cytoplasmic proteins - NEDD4-1, NDFIP1, and UBE2E1 - combine to tag PTEN with the small molecule ubiquitin. PTEN tagged with multiple ubiquitin molecules can then be recognized and destroyed by the cell's protein degradation machinery. Trotman and colleagues found that Importin-11 protects PTEN from degradation by escorting not only PTEN but also UBE2E1 into the nucleus, thereby breaking up the cytoplasmic ubiquitination apparatus.
Mice lacking Importin-11 showed lower levels of PTEN protein and developed lung adenocarcinomas and prostate neoplasias. Mutations in the gene encoding Importin-11 have been identified in human cancers, and Trotman and colleagues found that tumors from lung cancer patients lacking Importin-11 tended to show low PTEN levels as well. The researchers estimate that loss of Importin-11 may account for the loss of PTEN in approximately one third of lung cancer patients lacking this key anti-cancer protein.
In prostate cancer, loss of Importin-11 predicted disease relapse and metastasis in patients who had had their prostates removed. "We think that the degradation of PTEN after loss or impairment of Importin-11 is a very effective driver of human prostate cancer," says Trotman. "Our results suggest that Importin-11 is the "Achilles' heel" of the ubiquitination system that maintains the correct levels of PTEN inside cells."
Source: Eurekalert
PTEN Tumor Suppressor Gene Has Surprising New Insights
The PTEN gene which was first identified more than 15 years is known to play an integral role in preventing the onset and progression of numerous cancers.
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Scientists Identify New Type of Gene That Regulates Tumor Suppressor PTENA new so-called pseudogene that regulates the tumour-suppressing PTEN gene has been discovered by Karolinska Institute researchers. | Advertisement
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