STAT5

In order to be functional, STAT5 proteins must first be activated. This activation is carried out by kinases associated with transmembrane receptors: In the activation pathway illustrated to the left, the ligand involved is a cytokine and the specific kinase taking part in activation is JAK. The dimerized STAT5 represents the active form of the protein, which is ready for translocation into the nucleus. Once in the nucleus, the dimers bind to STAT5 response elements, inducing transcription of specific sets of genes. Upregulation of gene expression by STAT5 dimers has been observed for genes dealing with: == STAT5 and cancer ==

STAT5 has been found to be constitutively phosphorylated in cancer cells, • Inhibition of FLT3 is carried out by drugs like lestaurtinib • Inhibition of JAK2 is carried out by the drug CYT387, which was successful in preclinical trials and is currently undergoing clinical trials. Direct inhibition of STAT5 activity makes use of small molecule inhibitors that prevent STAT5 from properly binding to DNA or prevent proper dimerization. The inhibiting of DNA binding utilizes RNA interference, antisense oligodeoxynucleotide, The inhibition of proper dimerization, on the other hand, is brought about by the use of small molecules that target the SH2 domain. Recent work on drug development in the latter field have proved particularly effective. ==References==