The psammaplysenes, specific inhibitors of FOXO1a nuclear export.
A small collection of marine natural product extracts was screened for compounds that would compensate lost tumor suppressor functionality in PTEN-deficient cells. From the most active extract, the previously unreported bromotyrosine derivative, psammaplysene A (1), was identified. Psammaplysene A compensates for PTEN loss by relocalizing the transcription factor FOXO1a to the nucleus.
Schroeder
Frank C
FC
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kau
Tweeny R
TR
Silver
Pamela A
PA
Clardy
Jon
J
D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006801:Humans; D019156:Indian Ocean; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency* / Q000235:genetics; D011161:Porifera / Q000737:chemistry*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C501142:psammaplysene A; D014443:Tyrosine; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human