![Multifaceted pharmacologic targeting of FLT3-ITD via gene silencing, protein kinase inhibition and protein degradation. (A) Proteasome inhibitors disrupt the microRNA-29 (miR-29)/Sp1/nuclear factor κB (NF-κB) regulatory mechanisms of FLT3 gene transcription.5-7 (B) TKI inhibits FLT3 protein tyrosine kinase activity. (C) Proteasome inhibitors induces autophagy gene 5 (ATG5)/ATG12/ATG13-mediated autophagy, autophagosome formation (as indicated by the conversion of protein 1 light chain 3 [LC3-I] to LC3-II), and cargo protein–mediated FLT3-LC3 binding that ensure autophagic target degradation.8 P, phosphorylation.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/127/7/10.1182_blood-2015-09-666560/4/796f1.jpeg?Expires=1722424013&Signature=iq7NCGTm874200f9Hb6PNyadxcE~A755bEBLzt~Hw290wH9zWr1U1HGfDy~Weo2GLqAywG-9YfiGlT2h4seRkxrUYxOCwCkVSwU74IezklALODn53kldS0mnCORn4Sr3eDueyDEKhir-vl2zK5h9-An6WeFXu5oWXF3D8SNHHUMrjwk8JumvDfEHaRsI5PirIEkW3BMP1ZF0825Fw6vjBwgMO6T9cEj6ciOL8Tt8kK0qCCJN1yEHq9E-ck9jkUEayPetVgvsI~7dAgZEOGvR5H-0yGY3AefjlfxM~6Ip9Bbno2cZ9VwzQTypRkc9UCi91YguPER~FzxIOh~rwGNCqA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Multifaceted pharmacologic targeting of FLT3-ITD via gene silencing, protein kinase inhibition and protein degradation. (A) Proteasome inhibitors disrupt the microRNA-29 (miR-29)/Sp1/nuclear factor κB (NF-κB) regulatory mechanisms of FLT3 gene transcription.5-7 (B) TKI inhibits FLT3 protein tyrosine kinase activity. (C) Proteasome inhibitors induces autophagy gene 5 (ATG5)/ATG12/ATG13-mediated autophagy, autophagosome formation (as indicated by the conversion of protein 1 light chain 3 [LC3-I] to LC3-II), and cargo protein–mediated FLT3-LC3 binding that ensure autophagic target degradation.8 P, phosphorylation.
