c-MYC is an aggregation-prone, amyloidogenic protein

Area of Science:

• Molecular Biology
• Cell Biology
• Neuroscience

Background:

• c-MYC is a master transcription factor regulating numerous biological processes.
• c-MYC paradoxically acts as both an oncoprotein and a tumor suppressor by inducing apoptosis.
• The tumor suppressor role of c-MYC is not fully understood.

Purpose of the Study:

• To investigate the aggregation properties of c-MYC.
• To explore the potential link between c-MYC aggregation and its tumor suppressor activity.
• To understand the mechanism by which c-MYC amyloidogenesis induces apoptosis.

Main Methods:

• Investigated c-MYC aggregation under various conditions (heat shock, in vitro).
• Analyzed c-MYC structure in human cancer and Alzheimer's disease tissues.
• Screened c-MYC peptide library for amyloidogenic fragments.
• Assessed apoptosis induction independent of transcription.

Main Results:

• c-MYC is aggregation-prone, forming detergent-insoluble structures upon heat shock.
• c-MYC spontaneously forms soluble amyloid oligomers and protofibrils in vitro.
• Amyloidogenic c-MYC oligomers were found in human cancer and Alzheimer's disease brains.
• The dimerization partner MAX antagonizes c-MYC amyloidogenesis.
• Amyloidogenesis of c-MYC induces apoptosis largely independent of transcription.

Conclusions:

• c-MYC possesses previously unrecognized amyloidogenic properties.
• c-MYC amyloidogenesis may contribute to its tumor-suppressing activity.
• This amyloid formation could act as a failsafe mechanism against oncogenic c-MYC.
• Findings suggest a novel role for protein aggregation in cancer and neurodegenerative diseases.