Thalidomide and its metabolite 5‐hydroxythalidomide induce teratogenicity via the cereblon neosubstrate PLZF
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چکیده
منابع مشابه
Nitric oxide rescues thalidomide mediated teratogenicity
Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafi...
متن کاملGlutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon.
Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding...
متن کاملEvidence for the intercalation of thalidomide into DNA: clue to the molecular mechanism of thalidomide teratogenicity?
The intercalation of thalidomide (alpha-phthalimidoglutarimide) into nucleic acids was studied by spectrophotometric titrations, displacement of known intercalators, viscosity changes of DNA solutions, and by phase partition analysis. Specific binding of thalidomide was found to DNA of various specimens (human placenta, calf thymus, salmon sperm), but not to RNA (from bakers yeast, torula yeast).
متن کاملIdentification of a primary target of thalidomide teratogenicity.
Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN for...
متن کاملWhat is the functional role of the thalidomide binding protein cereblon?
It has been found that nonsense mutation R419X of cereblon (CRBN) is associated with autosomal recessive non-syndromic mental retardation. Further experiments showed that CRBN binds to the cytosolic C-terminus of large-conductance Ca(++) activated potassium channel (BK(Ca)) α-subunit and the cytosolic C-terminus of a voltage-gated chloride channel-2 (ClC-2), suggesting that CRBN may play a role...
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ژورنال
عنوان ژورنال: The EMBO Journal
سال: 2021
ISSN: 0261-4189,1460-2075
DOI: 10.15252/embj.2020105375