The proto-oncogene MYC is one of those factors studied in thousands of papers.
MYC and its dimerize partner MAX are also seemingly involved in just about everything. They have crucial roles in many kinds of stem cells including adult and embryonic stem cells. One way or another MYC induction seems very helpful for cellular reprogramming too.
I first really dove into studying MYC and by extension MAX as a postdoc in Bob Eisenman’s lab at The Hutch. I loved being a postdoc and having the opportunity to do all kinds of cool research. My work then included studies of MYC, MYCN, and the corepressor SIN3. With this background, I often find myself drawn to papers related to MYC so a new one related in part to digit development got my attention.
MYC and MAX
A recurrent de novo MAX p.Arg60Gln variant causes a syndromic overgrowth disorder through differential expression of c-Myc target genes, The American Journal of Human Genetics. One phenotypic take-home from this paper is: “Affected individuals have a complex disorder consisting primarily of macrocephaly, polydactyly, and delayed ophthalmic development.”
This one caught my eye in part because MYCN, which also dimerizes with MAX, has ties to digit developmental as well as polydactyly and syndactyly. For example, this old paper with my postdoctoral colleague and friend Peter Hurlin first made this MYCN connection. Activities of N-Myc in the developing limb link control of skeletal size with digit separation, Development. The macrocephaly part is intriguing too as MYC family loss of function, particularly for MYCN, causes the opposite: microcephaly. We first reported the role of MYCN loss of function in microcephaly in our 2002 G&D paper. Shortly after that, it was found that MYCN mutations cause microcephaly in humans. It was kind of amazing to see the connection between our mouse knockout work and a clinical syndrome in people.
I want to take this moment to thank an amazing senior scientist in Bob’s lab, Pei Feng Cheng, who was a major contributor to many of the studies on MYC family proteins.
More reads
- The maintenance of oocytes in the mammalian ovary involves extreme protein longevity, Nat Cell Bio.
- Shinya Yamanaka, Cell. This is a nice new interview. His biggest surprise? “I have been most surprised by how similar induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are.” What is he now most excited about? “I am most excited about the various applications of iPSCs. There are two major clinical applications: regenerative medicine and drug discovery. More than 20 clinical trials are ongoing for these applications.” On trust in science: “I think that interest in science among society is lower in Japan than in the US and some other countries. I have been doing my bit to change this situation. For example, I was involved in a series of TV programs named “Jintai,” which means “human body” in English, together with a famous TV personality. I was very happy when I met a student who told me she decided to go to medical school because of the TV program.” I did not realize this possible lower level of interest in science in Japan.
- Brain Chimeroids reveal individual susceptibility to neurotoxic triggers, Nature.
- Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy, Neuron.
- Enhancement of erythropoietic output by Cas9-mediated insertion of a natural variant in haematopoietic stem and progenitor cells, Nat. Biomed Engin. One possible worry is that enhanced output could predispose to malignancy.