(원문: 여기를 클릭하세요~)
Science 14 Sep 2018:
Vol. 361, Issue 6407, pp. 1084-1085
DOI: 10.1126/science.361.6407.1084-c
Off-label use of thalidomide became a worldwide trend in the 1950s and early 1960s to alleviate morning sickness. It resulted in a historical tragedy, as thousands of babies were born with severe birth defects. Donovan et al. may have found a missing link to explain how the drug affects fetal development. The researchers show that thalidomide and closely related drugs rapidly degrade the transcription factor Sal-like protein 4 (SALL4), which is necessary for fetal limb and organ formation. Adding further weight to their findings, certain individuals with mutations in the SALL4gene develop abnormalities that resemble thalidomide-induced birth defects.
eLife 7, e38430 (2018).
https://www.nature.com/articles/s41589-018-0134-0?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+nchembio%2Frss%2Fcurrent+%28Nature+Chemical+Biology+-+Issue%29
A new target for thalidomide
Nature Chemical Biology volume 14, pages 904–905 (2018) | Download Citation
One mechanism of thalidomide teratogenicity involves binding to the CUL4–CRBN E3 ubiquitin ligase complex, which then mediates the degradation of transcription factors. New studies reveal that species-specific variants of the transcription factor SALL4 are differentially ubiquitinated and degraded via the thalidomide-bound complex.