How symbiosis between two proteins keep organs cancer free

How symbiosis between two proteins keep organs cancer free


The mechanisms that orchestrate the functions of our bodies and keep us healthy are quite complex, involving critical molecular components that are still poorly understood. The prestigious journal Nature Communications has published recent research on this topic. Their work highlighted the crucial role played by a very specific protein, known as BAP1, in preventing cancer from developing.

Decades of research have shown that each of our cells is like a factory employing thousands of workers (who are, in this case, active proteins with highly specific roles and clearly defined life spans). Inside each cell, proteins communicate with one another so they can carry out their respective functions in perfect harmony. Any disruption in the way they work could lead to serious illnesses such as cancer. BAP1 plays a key role in protecting cells against cancer development--but, like other proteins, this tumour-suppressor can stop working properly. In fact, BAP1 defects are seen in many types of cancer, including mesothelioma, melanoma and renal cell carcinoma. For example, BAP1 malfunctions have been found in one half of patients suffering from mesothelioma, a particularly deadly form of cancer. The team had previously shown that BAP1 needs partners to remain operational and effectively protect cells, but the exact molecular mechanism of how it works remained unknown.

Using advanced scientific techniques, the team was able to gain a better understanding of certain tumor suppression mechanisms, revealing the molecular symbiosis between BAP1 and its partner ASXL2. This mutually beneficial relationship helps protect cells and, as a result, keep organs cancer-free.

Authors show that BAP1 promotes  DEUBiquitinase Adaptor (DEUBAD)  monoubiquitination resulting in an increased stability of ASXL2, which in turn stimulates BAP1 DUB activity. ASXL2 monoubiquitination is directly catalyzed by UBE2E family of Ubiquitin-conjugating enzymes and regulates mammalian cell proliferation. Remarkably, Calypso also regulates Asx monoubiquitination and transgenic flies expressing monoubiquitination-defective Asx mutant exhibit developmental defects. Finally, the protein levels of ASXL2, BAP1 and UBE2E enzymes are highly correlated in mesothelioma tumors suggesting the importance of this signaling axis for tumor suppression.

This research helps us understand how proteins work together and identifies critical protein communication points where breakdowns can lead to cancer. These insights could lead to new cancer diagnosis and treatment strategies, which could in turn significantly improve survival rates among patients with mesothelioma or other cancers. Understanding how communication failures between BAP1 and ASXL2 manifest at the molecular level could make personalized medicine possible.