title: Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140.
abstract: Human nucleolar phosphoprotein p140 (hNopp140) is a nucleolar phosphoprotein that can bind to doxorubicin, an anti-cancer agent. We have examined the interaction between hNopp140 and doxorubicin as well as the folding property of hNopp140. Also, the effects of ATP and phosphorylation on the affinity of hNopp140 to doxorubicin are investigated by affinity dependent co-precipitation and surface plasmon resonance methods. Doxorubicin preferentially binds to un-phosphorylated form of hNopp140 with a KD value of 3.3 x 10(-7) M. Furthermore, doxorubicin reduces the protein kinase CK2-dependent phosphorylation of hNopp140, indicating that doxorubicin may perturb the cellular function of hNopp140 by reducing the protein kinase CK2-dependent phosphorylation of hNopp140. Low contents of the secondary structures of hNopp140 and the fast rate of proteolysis imply that hNopp140 has a high percentage of flexible regions or extended loop structures.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1, Hwawolkok-dong, Songbuk-gu, Seoul 136-791, Korea.
authors.forename: Yun-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Won Kyu
authors.initials: WK
authors.lastname: Lee
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Jin
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.forename: Yeon Gyu
authors.initials: YG
authors.lastname: Yu
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011489:Protein Denaturation
chemical_list: C075564:NOLC1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D004317:Doxorubicin; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase