Driving apoptosis; MIB2, an E3 ligase protein to the cockpit!

Apoptosis is a highly regulated process of programmed cell death that occurs in multicellular organisms to eliminate unwanted and/or damaged cells. Apoptosis is therefore crucial for the maintenance of healthy function.

In many cancers, the pathways that regulate apoptosis can be affected resulting in uncontrolled cell growth. Hence, to understand and better treat cancers it is crucial to understand how these pathways function.

Nakabayashi et al identified Mind bomb 2 (MIB2), a ligase protein that is involved in the signalling pathway that leads to apoptosis. MIB2 is responsible for the suppression of protein-kinase 1 (RipK1) resulting in suppression of regulated cell death. Using AlphaScreening, the mechanism of apoptosis suppression by MIB2 was shown to occur by ubiquitylation of cellular FLICE-inhibitory protein (cFLIPL) which interrupts the RIPK1 kinase activity.

To quantify and identify ubiquitylation of cFLIPL by MIB2, HeLa cells were grown with the MIB2 knockout gene and compared to wild-type HeLa cell lines. The HeLa samples were digested and analysed by LC-MS/MS using IonOpticks Aurora Series columns. Here, the authors demonstrate that peptides of cFLIPL from the MIB2 knockout showed less ubiquitylation than the wild type indicating that MIB2 is responsible for ubiquitylation of cFLIPL. The data shown here demonstrates that MIB2 can alter RIPK1 kinase activity and suppress apoptosis.

Read the full paper
MIND bomb 2 prevents RIPK1 kinase activity-dependent and-independent apoptosis through ubiquitylation of cFLIP L.
Communications Biology 4, no. 1 (2021): 1-19. doi: https://doi.org/10.1038/s42003-020-01603-y
Nakabayashi, Osamu, Hirotaka Takahashi, Kenta Moriwaki, Sachiko Komazawa-Sakon, Fumiaki Ohtake, Shin Murai, Yuichi Tsuchiya et al.

Commentary by Muhammad Zenaidee, PhD

About the author
Muhammad holds a PhD in Chemistry from The University of New South Wales and has a strong background in the development of tools to enhance top-down and bottom-up proteomics. As an Application Scientist at IonOpticks, he utilises his knowledge and training to develop new proteomics tools and technologies for the proteomics community.