Expression of the RAI gene is conducive to apoptosis: studies of induction and interference.
The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. It has been speculated that the RAI product induces apoptosis by blocking NF-kappaB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we report that the expression of RAI mRNA was increased in non-transformed lymphocytes and fibroblasts induced to undergo apoptosis by various means, such as treatment with etoposide, calcium ions, or interleukin-2 and/or serum deprivation. Treatment with etoposide increased the content of RAI protein, too, and caused it to translocate to the nucleus. Inhibition of RAI expression in lymphocytes and fibroblasts with siRNA reduced apoptosis, but treatment with the NF-kappaB-inhibiting substance sulfasalazine relieved this dependence. In the transformed cell line HEK-293 the association between RAI induction and apoptosis seemed broken. Thus, we hypothesize that RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells. Our results could be explained by a NF-kappaB mediated mechanism.
Laska
Magdalena J
MJ
Institute of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
Strandbygård
Dorthe
D
Kjeldgaard
Anette
A
Mains
Mette
M
Corydon
Thomas J
TJ
Memon
Ashfaque A
AA
Sørensen
Boe S
BS
Vogel
Ulla
U
Jensen
Uffe B
UB
Nexø
Bjørn A
BA
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D017405:Herpes Simplex Virus Protein Vmw65 / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins; D012460:Sulfasalazine / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D017405:Herpes Simplex Virus Protein Vmw65; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D012460:Sulfasalazine; D005047:Etoposide