Myc, Nicked

Wikipedia (Crystal structure of Myc and Max in complex with DNA.)

The paper

M. Conacci-Sorrell et al., “Myc-nick: a cytoplasmic cleavage product of Myc that promotes α-tubulin acetylation and cell differentiation,” Cell, 142:480-93, 2010. Free F1000 Evaluation

The finding

When Maralice Conacci-Sorrell joined Bob Eisenman’s lab at the Fred Hutchinson Cancer Research Center in Seattle, Washington, she started studying the transcription factor and major oncogene protein, Myc, and its role in cancer. But following up on an experimental anomaly, she discovered a new role for Myc in differentiation and cytoskeletal organization.

The antibody

Conacci-Sorrell was surprised to find a smaller version of the Myc protein on her Western blots. She noticed this protein present in the cell cytoplasm—which is strange because Myc should be confined to the nucleus. Despite doubts that her results were caused by a contamination, she continued to work on the protein as a...

The discovery

When she expressed the short Myc in cells that normally don’t have the myc gene she found it did not affect proliferation or survival, but rather made cells turn spindly by increasing microtubule stability. When she expressed the protein in myoblasts, it accelerated muscle differentiation.

The impact

Faculty Member Valera Vasioukhin says this finding, “teaches all of us something”: that scientists shouldn’t ignore small fragments of a protein because “it might have an interesting function.” Conacci-Sorrell is now making mouse models that can’t cleave Myc, to see how cleavage affects development and tumorigenesis in whole animals.

F1000 evaluators: V. Vaslioukhin (Fred Hutchinson Cancer Res Cen) • Y. Yamashita (U of Michigan)

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