Bcl-2 and CrmA have different effects on transformation, apoptosis and the stability of I kappa B-alpha in chicken spleen cells transformed by temperature-sensitive v-Rel oncoproteins.
The retroviral oncoprotein v-Rel is a member of the Rel/ NF-kappa B family of transcription factors. We have previously characterized two v-Rel mutants (v-G37E and v-R273H) that are temperature-sensitive (ts) for transformation and immortalization of chicken spleen cells in vitro. We have now constructed vectors for the co-expression of wild-type or ts mutant v-Rel proteins and the anti-apoptosis proteins Bcl-2 or CrmA. The formation of v-Rel-transformed colonies is enhanced in the presence of overexpressed Bcl-2. Moreover, co-expression of Bcl-2 suppresses apoptosis that is induced when ts v-Rel-transformed cells are shifted to the non-permissive temperature. However, co-expression of Bcl-2 in these cells does not affect ts functions of v-Rel, such as DNA binding and stabilization of I kappa B-alpha. In contrast, co-expression of CrmA does not suppress apoptosis, but does block an amino-terminal proteolysis of I kappa B-alpha that occurs in ts v-G37E-transformed cells shifted to the nonpermissive temperature, indicating that an ICE-like protease activity is not involved in apoptosis in these cells but is involved in proteolysis of I kappa B-alpha. In addition, CrmA can block cycloheximide-induced amino-terminal processing of I kappa B-alpha in spleen cells transformed by wild-type v-Rel. In summary, these results suggest that v-Rel immortalizes chicken spleen cells through a pathway that involves the Bcl-2 family of proteins, and suggest that one pathway of proteolysis of I kappa B-alpha involves an ICE-like protease.
White
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DW
Department of Biology, Boston University, Massachusetts 02215-2406, USA.
Gilmore
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TD
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D020572:Oncogene Proteins v-rel; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics*; D013154:Spleen / Q000473:pathology* / Q000821:virology; D013696:Temperature; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D020572:Oncogene Proteins v-rel; D019253:Proto-Oncogene Proteins c-bcl-2; D015682:Retroviridae Proteins, Oncogenic; D015843:Serpins; D014764:Viral Proteins; D000072000:NF-KappaB Inhibitor alpha; C074641:interleukin-1beta-converting enzyme inhibitor