title: Expression of the RAI gene is conducive to apoptosis: studies of induction and interference.
abstract: 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.
authors.affiliation: Institute of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Laska
authors.forename: Dorthe
authors.initials: D
authors.lastname: Strandbygård
authors.forename: Anette
authors.initials: A
authors.lastname: Kjeldgaard
authors.forename: Mette
authors.initials: M
authors.lastname: Mains
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Corydon
authors.forename: Ashfaque A
authors.initials: AA
authors.lastname: Memon
authors.forename: Boe S
authors.initials: BS
authors.lastname: Sørensen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Uffe B
authors.initials: UB
authors.lastname: Jensen
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
mesh_terms: 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
chemical_list: 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