Identification of a Primary Target of Thalidomide Teratogenicity
A basis for thalidomide teratogenicity is revealed and may contribute to the development of new thalidmide derivatives without teratogenic activity.
Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN
This work presents a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
Structure of the human Cereblon–DDB1–lenalidomide complex reveals basis for responsiveness to thalidomide analogs
- P. Chamberlain, A. López-Girona, B. Cathers
- BiologyNature Structural &Molecular Biology
- 1 September 2014
The crystal structure of human CRBN bound to DDB1 and the drug lenalidomide is presented and it is shown that a hydrophobic pocket in the thalidomid-binding domain (TBD) of CRBN accommodates the glutarimide moiety of lenalidmide, whereas the isoindolinone ring is exposed to solvent.
Comparative functional genomics revealed conservation and diversification of three enhancers of the isl1 gene for motor and sensory neuron-specific expression.
Lhx2 mediates the activity of Six3 in zebrafish forebrain growth.
Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos
It is shown that uncaging eng2a in the head region during early development causes a severe reduction in the size of the eye and enhanced development of the mid brain and the midbrain-hindbrain boundary at the expense of the forebrain.
Teratogenic effects of thalidomide: molecular mechanisms
The data suggest that thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting its ubiquitin ligase activity, which indicates a thalidmide-binding protein, cereblon (CRBN), as a primary target for thalidOMide teratogenicity.
An abnormal ketamine response in mutants defective in the ryanodine receptor gene ryr-1 (unc-68) of Caenorhabditis elegans.
Results presented here will be useful in studying the structure and function of ryanodine receptors in excitation-contraction coupling and in understanding the evolution of rytonodine receptor tissue specificity.
Cloning and Mapping of a Ryanodine Receptor Homolog Gene of Caenorhabditis elegans a
Salicylic Acid Induces Mitochondrial Injury by Inhibiting Ferrochelatase Heme Biosynthesis Activity
It is established that ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, is responsible for salicylic acid–induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function.