Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2018 Sep 25:7:e41002.
doi: 10.7554/eLife.41002.

Unlocking a dark past

Fernando Rodríguez-Pérez  1   2 , Michael Rape  1   2
Affiliations
Comment

Unlocking a dark past

Fernando Rodríguez-Pérez et al. Elife. .

Abstract

A transcription factor called SALL4 could be the missing link between thalidomide and the limb defects caused by the drug.

Keywords: Chemical Biology; Teratogenicity; Thalidomide; Transcription Factors; Ubiquitin; biochemistry; chemical biology; developmental biology; human.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Thalidomide, the transcription factor SALL4 and limb defects.
(A) In the absence of an immunomodulatory drug like thalidomide the CUL4CRBN complex (multiple colors) 'tags' a substrate (purple) for degradation by the proteasome (pale blue). SALL4 remains intact during this process and is therefore able to control the transcriptional activity of target genes to control robust embryonic limb development. (B) The presence of thalidomide results in SALL4 being tagged for degradation. The subsequent absence of SALL4 prevents the transcription of its target genes and thus likely interferes with limb development, as observed in thalidomide syndrome. iMiD: immunomodulatory drug.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

References

    1. Borozdin W, Wright MJ, Hennekam RC, Hannibal MC, Crow YJ, Neumann TE, Kohlhase J. Novel mutations in the gene SALL4 provide further evidence for acro-renal-ocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. Journal of Medical Genetics. 2004;41:e102. doi: 10.1136/jmg.2004.019505. - DOI - PMC - PubMed
    1. Brynner R, Stephens T. Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine. Basic Books; 2001.
    1. Churcher I. Protac-induced protein degradation in drug discovery: breaking the rules or just making new ones? Journal of Medicinal Chemistry. 2018;61:444–452. doi: 10.1021/acs.jmedchem.7b01272. - DOI - PubMed
    1. Donovan KA, An J, Nowak RP, Yuan JC, Fink EC, Berry BC, Ebert BL, Fischer ES. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray Syndrome. eLife. 2018;7:e38430. doi: 10.7554/eLife.38430. - DOI - PMC - PubMed
    1. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327:1345–1350. doi: 10.1126/science.1177319. - DOI - PubMed