Moffitt researchers discover new way to control the SETDB1 protein upregulated in cancer -
Cancer is a group of more than 100 different diseases. All are driven by the cells and genes that are beyond the normal process of division and begin their own plan to replicate in the body. Advances in genetics and molecular biology offer researchers a better understanding of genetic mutations and cell changes that can lead to cancer, and also how to use this information to develop measures and preventive therapies to target diseases.
Moffitt Cancer Center, a leader in molecular cancer research, and a research team led by Jia Fang, Ph.D., assistant member of the department of biology of the tumor, discovered a new how to control the activity of SETDB1, a protein that is often upregulated in cancer. Their results were published in the June issue 16 Molecular Cell .
The new mechanism to control protein function is called monoubiquitination. The proteins can be resolved through a process called ubiquitination, in which a ubiquitin molecule is added to a protein. modification of ubiquitin may give rise to a number of different effects. The addition of a large number of ubiquitin molecules can target a protein degradation, whereas the addition of a single ubiquitin molecule (to monoubiquitination) can lead to activation of signaling pathways proteins or other target protein for the ubiquitination. Ubiquitin is generally added to a protein by an orderly series of events - activation by an E1 enzyme, by conjugation E2 enzyme and ligation with a E3 enzyme
SETDB1 regulates the level of compaction of the DNA and gene expression .. SETDB1 When activated, the levels of target gene expression is repressed. Given its essential role in the control of gene expression, SETDB1 must be set precisely so that the molecular processes are working properly.
Moffitt researchers carried out molecular studies demonstrate for the first time that constitutively SETDB1 is modified by a single ubiquitin molecule. Event ubiquitination is mediated by enzymes E1 and E2, without the traditional participation of an E3 enzyme. Importantly, this monoubiquitination serves as an integral part of SETDB1 to make its activity and leads to inhibition of expression of the target gene.
"This is the first demonstration that a constituent monoubiquitination by complete E2 enzyme the function of a key enzyme. These results suggest that this enzyme E2 class is an attractive target for cancer therapeutics" said Fang.
Moffitt Cancer Center, a leader in molecular cancer research, and a research team led by Jia Fang, Ph.D., assistant member of the department of biology of the tumor, discovered a new how to control the activity of SETDB1, a protein that is often upregulated in cancer. Their results were published in the June issue 16 Molecular Cell .
The new mechanism to control protein function is called monoubiquitination. The proteins can be resolved through a process called ubiquitination, in which a ubiquitin molecule is added to a protein. modification of ubiquitin may give rise to a number of different effects. The addition of a large number of ubiquitin molecules can target a protein degradation, whereas the addition of a single ubiquitin molecule (to monoubiquitination) can lead to activation of signaling pathways proteins or other target protein for the ubiquitination. Ubiquitin is generally added to a protein by an orderly series of events - activation by an E1 enzyme, by conjugation E2 enzyme and ligation with a E3 enzyme
SETDB1 regulates the level of compaction of the DNA and gene expression .. SETDB1 When activated, the levels of target gene expression is repressed. Given its essential role in the control of gene expression, SETDB1 must be set precisely so that the molecular processes are working properly.
Moffitt researchers carried out molecular studies demonstrate for the first time that constitutively SETDB1 is modified by a single ubiquitin molecule. Event ubiquitination is mediated by enzymes E1 and E2, without the traditional participation of an E3 enzyme. Importantly, this monoubiquitination serves as an integral part of SETDB1 to make its activity and leads to inhibition of expression of the target gene.
"This is the first demonstration that a constituent monoubiquitination by complete E2 enzyme the function of a key enzyme. These results suggest that this enzyme E2 class is an attractive target for cancer therapeutics" said Fang.
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