title: Downregulation of beta1,4-galactosyltransferase 1 inhibits CDK11(p58)-mediated apoptosis induced by cycloheximide.
abstract: Cyclin-dependent kinase 11 (CDK11; also named PITSLRE) is part of the large family of p34(cdc2)-related kinases whose functions appear to be linked with cell cycle progression, tumorigenesis, and apoptotic signaling. The mechanism that CDK11(p58) induces apoptosis is not clear. Some evidences suggested beta1,4-galactosyltransferase 1 (beta1,4-GT 1) might participate in apoptosis induced by CDK11(p58). In this study, we demonstrated that ectopically expressed beta1,4-GT 1 increased CDK11(p58)-mediated apoptosis induced by cycloheximide (CHX). In contrast, RNAi-mediated knockdown of beta1,4-GT 1 effectively inhibited apoptosis induced by CHX in CDK11(p58)-overexpressing cells. For example, the cell morphological and nuclear changes were reduced; the loss of cell viability was prevented and the number of cells in sub-G1 phase was decreased. Knock down of beta1,4-GT 1 also inhibited the release of cytochrome c from mitochondria and caspase-3 processing. Therefore, the cleavage of CDK11(p58) by caspase-3 was reduced. We proposed that beta1,4-GT 1 might contribute to the pro-apoptotic effect of CDK11(p58). This may represent a new mechanism of beta1,4-GT 1 in CHX-induced apoptosis of CDK11(p58)-overexpressing cells.
authors.affiliation: State Key Laboratory of Genetic Engineering and Gene Research Center, Shanghai Medical College of Fudan University, Box 103, Shanghai 200032, People's Republic of China.
authors.forename: Zejuan
authors.initials: Z
authors.lastname: Li
authors.forename: Hanzhou
authors.initials: H
authors.lastname: Wang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zong
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Kong
authors.forename: Jianhai
authors.initials: J
authors.lastname: Jiang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008970:Molecular Weight; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference
chemical_list: D061945:Caspase Inhibitors; D007527:Isoenzymes; D045304:Cytochromes c; D003513:Cycloheximide; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I; D011065:Poly(ADP-ribose) Polymerases; D018844:Cyclin-Dependent Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases