The multifaceted proteins Reptin and Pontin as major players in cancer.

Reptin and Pontin belong to the family of AAA+ ATPases (ATPases Associated with various cellular Activities). Several studies have reported their overexpression in cancer, including hepatocellular carcinoma and colorectal cancer. Functional studies have implicated them in many cellular processes highly relevant to cancer. They thus interact with the oncogenes c-myc and β-catenin, and modulate their transcriptional activities. They participate in large molecular complexes such as the INO80 or the TIP60 complexes that are involved in chromatin remodeling or DNA damage repair. They are also required for the biogenesis of telomerase. Studies that used RNA interference or expression of mutated proteins have concluded at their role in cell growth and viability. Interestingly, not all their functions require an intact ATPase domain. Besides their roles as nuclear proteins, recent evidence suggests that they also have cytosolic functions such as regulation of the nonsense mediated decay of mRNAs. Finally, silencing experiments in xenografts indicate that they may be suitable targets for cancer therapy.