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New protein targets for cancer-ASK1
Update time:2018-03-12 00:50:28   【 Font: Large  Medium Small

          Recently, a study may be able to help us find the new treatment of cancer and neurodegenerative diseases. Atsushi Matsuzawa who is a professor from Japan with some people using gene silencing technology testing a small molecule mechanism of apoptosis signal-regulating kinase1(ASK1)

          ASK1 is an oxidative stress-responsive kinase that is regulated by various interacting molecules and post-translational modifications. However how these molecules and modifications cooperatively regulate ASK1activity remains largely unknown.ASK1 in responses to various types of stresses including oxidative stress, and subsequently induces multiple cellular responses, such as cell death and inflammation.

          Protein arginine methyltransferase1(PRMT1)which negative regulates ASK1 activation by enhancing its interaction with thioredoxin (Trx) another ASK1-negative regulator.TRIM48 facilitates ASK1 activation by promoting k48-linked poly ubiquitination and degradation of PRMT1.TRIM48 knockdown suppressed oxidative stress-induced ASK1 activation and cell death ,whereas forced expression promoted cancer cell death, whereas forced expression promoted cancer cell death in mouse xenograft model. These results indicate that TRIM48 facilitates oxidative stress-induced ASK1activation and cell death through ubiquitination dependent degradation of PRMT1

          The study provides a cell death mechanism fine-tuned by the crosstalk between enzymes that engage various types of post-translational modifications. In the future, if we can reveal mechanism of ASK1, it will get great development for the treatment of diseases.


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