title: Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells.
abstract: Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucidated. Here we demonstrate that IKAP/hELP1 depleted colon cancer-derived cells show enhanced basal expression of some but not all pro-apoptotic p53-dependent genes such as BAX. Moreover, Elongator deficiency causes increased basal and daunomycin-induced expression of the pro-survival serum- and glucocorticoid-induced protein kinase (SGK) gene through a p53-dependent pathway. Thus, our data collectively demonstrate that Elongator deficiency triggers the activation of p53-dependent genes harbouring opposite functions with respect to apoptosis.
authors.affiliation: Unit of Signal Transduction, Interdisciplinary Cluster for Applied Genoproteomics, University of Liège, Sart-Tilman, B-4000 Liège, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cornez
authors.forename: Catherine
authors.initials: C
authors.lastname: Creppe
authors.forename: Magali
authors.initials: M
authors.lastname: Gillard
authors.forename: Benoît
authors.initials: B
authors.lastname: Hennuy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chapelle
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dejardin
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Merville
authors.forename: Pierre
authors.initials: P
authors.lastname: Close
authors.forename: Alain
authors.initials: A
authors.lastname: Chariot
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004249:DNA Damage; D003630:Daunorubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000172:deficiency*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D003630:Daunorubicin; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D035602:Transcriptional Elongation Factors; D016159:Tumor Suppressor Protein p53; D000099184:Serum-Glucocorticoid Regulated Kinases; C114720:Elp1 protein, human