c-MYC is an aggregation-prone, amyloidogenic protein

Authors

Lin, L., Chuang, K.-H., Dai, C.

Abstract

As a master transcription factor, c-MYC governs a plethora of biological processes. Despite being a prominent oncoprotein, counterintuitively, c-MYC also possesses an intrinsic tumor suppressor activity through induction of apoptosis, a phenomenon known as "the paradox of c-MYC". Serendipitously, we discover that c-MYC is aggregation-prone, becoming detergent-insoluble upon heat shock. Even in the absence of heat shock, c-MYC assembles into soluble oligomers exhibiting characteristics of amyloids in both human cancer tissues and, surprisingly, human Alzheimer's disease brains. In vitro, recombinant c-MYC proteins form amyloid oligomers as well as protofibrils spontaneously. By contrast, its obligate dimerization partner MAX is non-amyloidogenic and, moreover, antagonizes the amyloidogenesis of c-MYC. Screening of the c-MYC synthetic peptide library identifies two intrinsically disordered short linear fragments, which are amyloidogenic in vitro. This amyloidogenesis of c-MYC, importantly, induces apoptosis largely independently of transcription. Thus, our findings unveil a previously unrecognized amyloidogenicity of c-MYC, which may contribute to its tumor-suppressing activity. Upon loss of the stringent control of its expression, conceptually, this amyloidogenesis of c-MYC may serve as a built-in failsafe mechanism to self-destruct its troublesome oncogenic potential.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 14 Mar 2026.

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