Decreased protein levels of the c-Cbl protooncogene in murine AIDS.
Murine acquired immunodeficiency syndrome (MAIDS) can be viewed as a lymphoproliferative disease which involves B cells as well as T cells from spleen and lymph nodes while thymus and Peyer's patches do not participate in the process. The 120-kDa protooncogene product c-Cbl was initially cloned from the murine Cas NS-1 B cell lymphoma. It is a main target of immunoreceptor (TCR and BCR)-mediated protein tyrosine kinase activity. Moreover, recent data suggest that c-Cbl might play a crucial role in the regulation of cell proliferation through regulation of GTP-binding proteins. Therefore, the involvement of c-Cbl was evaluated in the lymphoproliferative disease induced by the MAIDS virus. The expression of the c-Cbl protein was dramatically reduced in the lymph node of infected mice while it remained normal in the thymus. In contrast, the expression of actin, TCR-zeta chain, ZAP-70, and p59(fyn) remained similar in controls and infected mice. Identical results were obtained with sorted B cells and T cells. Surprisingly, a B cell lymphoma line derived from late stage MAIDS mice displayed a normal level of c-Cbl.
Trebak
M
M
Laboratory of Pathology, University of Liège, Liège, 4000, Belgium.
Lambert
C A
CA
Rahmouni
S
S
Debrus
S
S
Defresne
M P
MP
Regnier
D
D
Boniver
J
J
Moutschen
M
M
D000818:Animals; D015536:Down-Regulation; D008198:Lymph Nodes / Q000737:chemistry; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl; D012333:RNA, Messenger / Q000032:analysis; D013950:Thymus Gland / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C493849:Cbl protein, mouse