Title:
Preservation of ESC pluripotency without Myc activity

Akihiko Okuda, M.D.,Ph.D.
Division of Developmental Biology, Research Center for Genomic Medicine,
Saitama Medical University

Abstract:
Mycfamily comprises of three very related proteins called c-Myc, N-Myc and L-Myc and all these proteins require Max protein as an obligate partner for exerting their transcriptional stimulating activity. Like Oct3/4, accumulating evidence has placed Myc proteins at the heart of the regulatory network that governs pluripotent state of ESCs. Consistent with this notion, we have previously demonstrated that homozygous knockout of Max gene in ESCs led to the loss of ESC pluripotency. At the same time, we also found that ESCs under ground state condition are able to preserve pluripotent state even in the absence of Max expression, suggesting that, unlike Oct3/4, Myc is not an absolute, but context dependent regulator of ESC status.
During these studies, we encountered an unexpected additionalphenomenon associated with Maxexpression ablation. Only our Max -null ESCs, but not c-Myc/N-Myc double knockout ESCs, show extensive cell death, although both two ESC lines were generated for the same purpose, i.e., deprivation of Myc activity. In the seminar, I will present unique role of c-Mycprotein free from Max which was uncovered during our trial of understanding a possible cause of cell death phenotype of Max -null ESCs.

References:
Hishida T, Nozaki Y, Nakachi Y, Mizuno Y, Okazaki Y, Ema M, Takahashi S, Nishimoto M, Okuda A. Indefinite self-renewal of ESCs through Myc/Max transcriptional complex-independent mechanisms. Cell Stem Cell 9:37-49, 2011

Hishida T, Nozaki Y, Nakachi Y, Mizuno Y, Iseki H, Katano M, Kamon M, Hirasaki M, Nishimoto M, Okazaki Y, Okuda A. Sirt1, p53 and p38MAPK are crucial regulators of detrimental phenotypes of ESCs with Max expression ablation. Stem Cells 30:1634-1644, 2012 .