Ribosomal proteins: functions beyond the ribosome.

Although ribosomal proteins are known for playing an essential role in ribosome assembly and protein translation, their ribosome-independent functions have also been greatly appreciated. Over the past decade, more than a dozen of ribosomal proteins have been found to activate the tumor suppressor p53 pathway in response to ribosomal stress. In addition, these ribosomal proteins are involved in various physiological and pathological processes.

Scission of the p53-MDM2 Loop by Ribosomal Proteins.

The oncoprotein MDM2 is both the transcriptional target and the predominant antagonist of the tumor suppressor p53. MDM2 inhibits the functions of p53 via a negative feedback loop that can be circumvented by several ribosomal proteins in response to nucleolar or ribosomal stress. Stress conditions in the nucleolus can be triggered by a variety of extracellular and intracellular insults that impair ribosomal biogenesis and function, such as chemicals, nutrient deprivation, DNA damaging agents, or genetic alterations.