Research Highlights in 2011

Pyruvate kinase catalyzes the transfer of a high-energy phosphate group from phosphoenol pyruvate (PEP) to generate pyruvate and ATP, a reaction that is the rate-limiting step of the glycolytic pathway. The PKM1 alternatively-spliced isoform is ubiquitously expressed whereas the PKM2 isoform is normally highly expressed only in embryos and undifferentiated tissues, correlating with high rates of cellular proliferation. Notably, tumors express the PKM2 form to the exclusion of the M1 isoform.

We all have been taught that the immune system is educated in the thymus; however, where the immune system receives the second lesson in order to be tolerant against non-harmful pathogens, such as commensal bacteria, has never been addressed. Considering that commensal bacteria colonize the intestine and that regulatory T (Treg) cells are enriched in this organ, one could think that the intestine is the place where this second lesson would occur. This idea was now sustained by the work of Lathrop et al., which sheds new light on the complex mechanism of peripheral tolerance induction.

Gene-editing technologies and patient-specific induced pluripotent stem cells (iPSCs) may represent an unprecedented opportunity for merging the stem cell and traditional gene therapy fields to fulfill the promises of regenerative medicine.

The CTCF/cohesin complex regulates higher order chromatin structure by creating long-range chromatin loops and by insulating neighboring genes from each other. The lymphocyte antigen receptor loci have large numbers of CTCF/cohesin binding sites, and recent studies demonstrate that the CTCF/cohesin complex plays several important roles in regulating the process of V(D)J recombination at these megabase-sized receptor loci.

Shh and Wnts, secreted by the floor and roof plate of the spinal cord, direct longitudinal growth of the axons from the adjacent ventral funiculus and cortico-spinal tract. Whether these midline cues influence the directionality of axons elongating in more lateral positions of the spinal cord is unexplored. Song and colleagues investigate this possibility and demonstrate that the location of descending raphe-spinal tract in the ventrolateral spinal cord is dictated by the simultaneous repellent activity of Shh gradients in both the anterior-to-posterior (A-P) and medial-to-lateral (M-L) axis.

It is well documented that the K-RAS oncogene efficiently transforms non-malignant cells, and there is some evidence for the role of mitochondria in this process. Now Peng Huang and colleagues show that K-Ras induction results early on in mitochondria assuming the phenotype consistent with the so-called Warburg effect, i.e., increased glycolysis and attenuated oxidative phosphorylation. Thus the K-Ras protein capable of swift induction of phenotypic changes typical of cancer cells, yet these changes are reversible, and for cells to irreversibly reach their full malignant potential a much longer K-Ras expression is required, implicating mitochondria in the longer-term effects of the oncogene.