The Regulation of Autophagy and Its Role in Mitotic Exit

Autophagy is an evolutionarily conserved pathway in which cells enclose cytoplasmic contents in double membrane vesicles and deliver them to the lysosome for degradation. Autophagy plays critical regulatory roles in cancer, aging, neurodegeneration, immunity and many other physiological processes. Autophagy can be induced by multiple conditions such as starvation, viral infection, exercise and oxidative stress. In this work, we studied the role of autophagy in starvation-induced cell cycle arrest and quiescence entry, and studied the function and regulation of a major phosphorylation site of Beclin 1, serine 90. In the first study, we found that the in response to starvation, autophagy-deficient yeasts failed to arrest properly in G1/G0, but arrested in telophase with a quiescent-specific phenotype. In a second study, we found that Beclin 1 serine 90 is a major phosphorylation site of Beclin 1, which is induced by multiple stresses such as starvation and osmotic stress. The phosphorylation of Beclin 1 serine 90 leads to the activation of autophagy and inhibition of tumorigenesis. We identified MK2/3 as kinases that positively regulate autophagy by phosphorylating Beclin 1 at amino acid residue serine 90. We also found that Beclin 1 serine 90 phosphorylation is negatively regulated by Bcl-2 and positively regulated by AMPK. Beclin 1 serine 90 phosphorylation is also important for cell survival during high osmotic stress. Taken together, these results suggest that Beclin 1 serine 90 phosphorylation is a critical event in autophagy induction, which is tightly regulated by multiple kinases and regulatory proteins.

Author dc:creator

• An, Zhenyi

Contributors dc:contributor

• Tu, Benjamin
• Cobb, Melanie H.
• White, Michael A.

• Apoptosis Regulatory Proteins
• Autophagy
• Mitogen-Activated Protein Kinases
• Phosphorylation

Language dc:language

en

Identifier

957676331

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/3582