Investigators at the UC Davis Schools of Medicine and Veterinary Medicine, dig out a complicated relationship between p53 and another protein, Rbm38, highlighting how the body calibrates protein levels. Too much Rbm38 reduces p53 levels, increasing the risk of cancer. The finding was published in the journal PNAS.

As known long, the p53 protein is necessary for tumor suppression.When Rbm38 suppresses p53, organisms develop tumors. Knocking out Rbm38 increases p53, which might be considered as a good thing. But too much p53 suppresses cell-cycle progression, causing cell death, premature aging and even cancer.

Scientists regarded the relationship between p53 and Rbm38 as a loop: p53 regulates Rbm38 expression, while Rbm38 suppresses p53. There are contradictory results that Higher Rbm38 levels have been found in certain breast and colorectal cancers and dog lymphoma. However, increased Rbm38 is also associated with better prognoses in glioblastoma, ovarian cancer and other forms of breast cancer.

What would happen if Rbm38 was removed?

They found that knocking out Rbm38, and thus increasing p53, caused problems with blood formation, increased sensitivity to ionizing radiation and premature aging. Also, they found that increased p53 levels cause apoptosis, which leads to shorter lifespans. Perhaps most surprising, the animals also had increased cancer risk, boosted by the accelerated aging.

These intricate interactions are cause for both caution and excitement. While too much p53 can be a bad thing, carefully manipulating these two proteins could have therapeutic benefits.

The mutual regulation between Rbm38 and p53 is critically important to both aging and tumorigenesis. It’s possible to make p53 levels go up in tumor cells via targeting Rbm38 , which could kill tumor cells and suppress cancer progression.

Reference:

Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors. PNAS, December 2014