Jan 8, 2008

Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression, and stimulation of caspase-dependent cell death

Molecular and Cellular Biology
Jürgen KnoblochUlrich Rüther


Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (Bmps) protects active PTEN from proteasomal degradation, resulting in suppression of Akt signaling. As a consequence, caspase-dependent cell death is stimulated by the intrinsic and Fas death receptor apoptotic pathway. Most importantly, thalidomide-induced limb deformities and microphthalmia in chicken embryos could be rescued by a pharmacological PTEN inhibitor as well as by insulin, a stimulant of Akt signaling. We therefore conclude that perturbation of PTEN/Akt signaling and stimulation of caspase activity is central to the teratogenic effects of thalidomide.

  • References
  • Citations3


  • We're still populating references for this paper, please check back later.

Mentioned in this Paper

Biochemical Pathway
Central Nervous System Stimulant [EPC]
Central Nervous System Stimulants
Apoptosis, Intrinsic Pathway
Receptor Down-Regulation
Paracrine Protein Factors
Protein kinase B gamma
Bone Morphogenetic Proteins
Limb Structure

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jürgen KnoblochUlrich Rüther
Proceedings of the National Academy of Sciences of the United States of America
Christina TherapontosNeil Vargesson
Birth Defects Research. Part A, Clinical and Molecular Teratology
Sarah E Ali-Khan, Barbara F Hales
© 2020 Meta ULC. All rights reserved