Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by radicicol, a SRC-kinase inhibitor.
Radicicol, an inhibitor of src or src-like kinases, causes hypophosphorylation and down-regulation of the RB retinoblastoma tumor suppressor protein in HL-60 human promyelocytic leukemia cells. Both of these changes in the RB protein typically are associated with myeloid or monocytic differentiation of these cells induced by retinoic acid or 1,25-dihydroxy vitamin D3. When added with either inducer, radicicol caused the typically induced myeloid or monocytic differentiation of these cells to be accelerated. By itself radicicol caused a transient inhibition of G1 to S transit, but did not cause phenotypic conversion. The down-regulation and dephosphorylation of RB by radicicol may thus facilitate cell differentiation.
Yen
A
A
Department of Pathology, Cornell University, Ithaca, New York 14853.
Soong
S
S
Kwon
H J
HJ
Yoshida
M
M
Beppu
T
T
Varvayanis
S
S
D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D018942:Macrolides; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007783:Lactones; D018942:Macrolides; D016160:Retinoblastoma Protein; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D002117:Calcitriol; C035359:monorden