Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells.
Elife
; 102021 01 21.
Article
em En
| MEDLINE
| ID: mdl-33475085
Cancer is a complex illness where changes inside healthy cells causes them to grow and reproduce rapidly. Specialized proteins called enzymes which regulate chemical reactions in the cell often help cancer develop and spread through the body. One such enzyme called PARP-7 labels other proteins by attaching a chemical group which changes their behavior. However, it was unknown which proteins PARP-7 modifies and how this tag alters the actions of these proteins. To investigate this, Parsons, Challa, Gibson et al. developed a method to find and identify the proteins labelled by PARP-7 in ovarian cancer cells taken from patients and cultured in the laboratory. This revealed that PARP-7 labels hundreds of different proteins, including adhesion proteins which affect the connections between cells and cytoskeletal proteins which regulate a cell's shape and how it moves. One of the cytoskeletal proteins modified by PARP-7 is α-tubulin, which joins together with other tubulins to form long, tube-like structures known as microtubules. Parsons et al. found that when α-tubulin is labelled by PARP-7, it creates unstable microtubules that alter how the cancer cells grow and move. They discovered that depleting PARP-7 or mutating the sites where it modifies α-tubulin increased the stability of microtubules and slowed the growth of ovarian cancer cells. Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. A new drug which suppresses the activity of PARP-7 has recently been developed, and this drug could potentially be used to treat ovarian cancer patients with high levels of PARP-7. Clinical trials are ongoing to see how this drug affects the behavior of cancer cells in patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte de Nucleosídeos
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ADP-Ribosilação
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Microtúbulos
Tipo de estudo:
Diagnostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article