Inhibition of p53, p21 and Bax by pifithrin-alpha does not affect UV induced apoptotic response in CS-B cells.
Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. In spite of a TCR deficiency at the cellular level, CS patients do not develop cancer. The lack of cancer incidence in CS patients may be due to the selective elimination of cells by an apoptotic pathway. In order to verify the role of p53-associated pathway in ultraviolet (UV) induced apoptosis in human CS-B cells, the expression of p53 and p53 responsive genes was analysed in UV irradiated human cells after treatment with pifithrin-alpha (PFTalpha). PTFalpha effectively inhibited the induction of p53, p21 and Bax after UV treatment without affecting the apoptotic response in CS-B cells. Our results indicate that the p53-associated pathway involving p21 and Bax does not largely contribute to UV induced apoptosis in TCR defective human CS-B cells.
Proietti De Santis
Luca
L
Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, Università degli Studi della Tuscia, 01100 Viterbo, Italy.
Balajee
Adayabalam S
AS
Lorenti Garcia
Claudia
C
Pepe
Gaetano
G
Worboys
Ana Montes
AM
Palitti
Fabrizio
F
D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D052160:Benzothiazoles; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles / Q000494:pharmacology*; D014050:Toluene / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*
C494826:BAX protein, human; D052160:Benzothiazoles; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014050:Toluene; C121565:pifithrin; D020741:rho GTP-Binding Proteins