A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization

Article Abstract:

The importance of Large Tumor Suppressor 2 (Lats 2), which binds Mdm2, inhibits its E3 ligase activity and activates p53, is described. Abrogation of Lats2 promotes accumulation of polyploid cells upon exposure to nocodazole, which can be prevented by direct activation of p53 and the Lats2-Mdm2-p53 axis thus constitutes a novel checkpoint pathway critical for the maintenance of proper chromosome number.

Japan, Research and Development in the Physical, Engineering, and Life Sciences, Research and Testing Services, Cancer & Cell R&D, Health aspects, Cancer research, Cancer, Ploidy, Oncology, Experimental

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ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor

Article Abstract:

An ubiquitin ligase, ARF-BP1, is identified as the key factor associated with ARF in vivo to understand the mechanism of ARF-mediated tumor suppression. ARF-BP1 is a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF and ARF-Bp1 serves as a potential target for therapeutic intervention in tumors regardless of p53 status.

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Life, death, and ubiquitin: Taming the mule

Article Abstract:

The E3 ubiquitin ligase plays an important role in ubiquitin-mediated protein degradation, which is an efficient way for the cell to get rid of unwanted proteins. A new E3 ligase, ARF-BP1/Mule is described, which targets two very different substrates, p53 and Mcl-1, with completely different cellular outcomes.

Proteolysis

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