Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells.
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.
Cornez
Isabelle
I
Unit of Signal Transduction, Interdisciplinary Cluster for Applied Genoproteomics, University of Liège, Sart-Tilman, B-4000 Liège, Belgium.
Creppe
Catherine
C
Gillard
Magali
M
Hennuy
Benoît
B
Chapelle
Jean-Paul
JP
Dejardin
Emmanuel
E
Merville
Marie-Paule
MP
Close
Pierre
P
Chariot
Alain
A
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
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