Antagonistic balance of proteins safeguard against cancer

The ribosomal proteins, Rpl22 and Rpl22-like1, are both crucial for the development of T-cells (a type of blood cell), and were previously thought to carry out identical functions. Researchers from the Fox Chase Cancer Center, Philadelphia, US, have found that they are in fact antagonists of each other. The antagonistic relationship between the two proteins control stem cell production, and play a key role in preventing cancer.

The study, published in Developmental Cell, used zebrafish to determine the functions of Rpl22 and Rpl22-like1 and their relationship to each other. Zebrafish were used as a model because the proteins in question are 73 % identical to the human ones. Each protein was selectively blocked in order to assess the function of the other, revealing that even though they both contribute to the development of T-cells, they do so by different mechanisms.

Knockdown of Rpl22-like1 blocked the emergence of stem cells, which further blocked the development of new T-cells. In contrast, knockdown of Rpl22 specifically blocked the development of a particular T-cell progenitor, but didn’t affect the production of stem cells. Despite the similar outcome of the two proteins, they were each unable to circumvent the block of T-cell production created by the knockdown of the other, suggesting that Rpl22 and Rpl22-like1 do not simply operate by different mechanisms, but carry out antagonistic functions.

Stem cell emergence is therefore regulated by Rpl22 and Rpl22-like1: predominance of Rpl22-like1 promotes stem cell production, and predominance of Rpl22 represses it. An elevation of Rpl22-like1 is often observed in patients with a variety of cancers – leukaemia in particular. A likely cause of cancer may be a disturbance in the balance between these proteins. Maintaining the antagonistic relationship between Rpl22 and Rpl22-like1 could hence be a way of preventing types of cancer in the future.

Reference: Zhang et al. (2013). Control of Hematopoietic Stem Cell Emergence by Antagonistic Functions of Ribosomal Protein Paralogs. Developmental Cell (24), 411-425.