Research Highlights in 2012

The ORAI1 store-operated calcium channel, also known as the CRAC channel, has provided many surprises. The latest is that channel gating and ion selectivity are closely intertwined.

The prevalence of certain driver mutations in prostate cancer varies across ethnic populations. A recent study uses RNA-seq to profile the mutational landscape of prostate cancer in a Chinese population to gain additional insights on ethnic variation in this disease.

The discovery of Nongken 58S, a natural recessive photoperiod-sensitive male sterile line, served as a starting point for development of two-line hybrid rice in China. While original Nongken 58S in its japonica background is photoperiod-sensitive male sterile, after introgressing of the related locus into indica rice background the same trait become mainly temperature-sensitive male sterile. Although those photoperiod- and temperature-sensitive male sterile lines have been successfully used in two-line hybrid rice seed production, the genetic cause remained a mystery till the two recent publications, with one in Cell Research.

LRRK2 was recently identified as a major susceptibility gene for Crohn's disease (CD) by genome-wide association studies (GWAS). LRRK2 deficiency in mice confers enhanced susceptibility to experimental colitis. In this research highlight, we discuss the current understanding of LRRK2 in the context of colitis, and postulate the future directions.

BECN1 plays a central role in determining cell fate, acting as a balance point in the decision to undergo autophagy or apoptosis. Three distinct structural domains allow BECN1 to interact with several other proteins. Recent crystallographic data provide insight into the nature of the coiled-coil and evolutionarily conserved domains.

Emerging evidence suggests an involvement of nuclear pore components in the regulation of neural differentiation and aging. These findings will have far-ranging impacts on the understanding of the function of the nuclear envelope in physiological settings and in various neurological diseases.

Induced pluripotent stem cells (iPSCs) and the cell transdifferentiation technologies are providing powerful tools to generate patient-specific cells for research and therapeutic applications. Hepatocytes and pancreatic β cells are two endoderm-derived cell types drawing much attention due to their indispensable physiological functions and strong association with various diseases. Recent advances in hepatocyte and β cell transdifferentiation have provided valuable insights into how to regenerate and restore normal functions of liver and pancreas under pathological conditions.

The zinc-finger DNA-binding protein CTCF has been known for being a constituent of insulators. A recent paper in Nature reports an unforeseen intragenic role for CTCF that links DNA methylation with alternative splicing. By binding to its target DNA site placed within an alternative exon, CTCF creates a roadblock to transcriptional elongation that favors inclusion of the exon into mature mRNA. DNA methylation prevents CTCF binding, which releases pol II transient blockage and promotes exon exclusion.

Protein kinases are arguably the most tractable candidates for development of new therapies to treat cancer. Deep sequencing of breast cancer cell lines indicates each express 375 or so kinases, representing nearly 75% of the kinome. A rich network both downstream and upstream from key oncogenic kinases includes both tyrosine and serine/threonine kinases, giving plasticity and resiliency to the cancer cell kinome.

Pre-leukemic MLL-AF4 fusions arise prenatally and typically lead to overt acute lymphoblastic leukemia (ALL) at or shortly after birth. In a recent study, Bueno and colleagues explored the effects of MLL-AF4 expression in human embryonic stem cells (hESCs), with a focus on early hemato-endothelial development.

In patients with malaria, Plasmodium falciparum parasites multiply to enormous numbers in the bloodstream, initiating processes of erythrocyte destruction, endothelial activation and microvascular inflammation that cause devastating pathological effects on host tissues and organs. Recent research casts new light on a mechanism by which hemoglobin mutations may protect against these effects, and on a critical receptor-ligand interaction that provides fresh opportunities for the development of vaccines against blood-stage infection.

Many cancer cells depend on glutamine as a fuel for proliferation, yet the mechanisms by which glutamine supports cancer metabolism are not fully understood. Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

A hallmark feature of pluripotent stem cells is the ability to proliferate indefinitely (immortal phenotype). Despite reactivation of telomerase during iPSC derivation, there exists considerable heterogeneity in telomere length amongst established iPSC cell lines. Both telomerase-dependent and -independent mechanisms have now been shown to be important for continuous self-renewal of iPSC via the maintenance or extension of telomere length.