Prohibitin expression is increased in phorbol ester-treated chronic leukemic B-lymphocytes.
Chronic lymphocytic leukemia (CLL) is characterized by the gradual accumulation of immature B-lymphocytes. CLL B-lymphocytes mature to a plasmacytoid phenotype when treated in vitro with phorbol esters. CLL B-cell apparent maturation is associated with altered expression of specific plasma membrane and mitochondrial proteins including heightened expression of a 30-kDa heat shock protein 60 (hsp60) analog. During our efforts to further characterize this hsp60 analog by mass spectrometry, we detected the mitochondrial protein prohibitin in phorbol-ester-matured CLL B-lymphocytes. Prohibitin modulates cell proliferation and inhibits cell cycle traverse in several systems, although few data are available for lymphocytes. A twofold increase in prohibitin concentration was observed in phorbol-ester-matured compared to resting CLL B-cells as determined by quantitative Western immunoblot analysis. A similar increase in prohibitin was observed in phorbol-ester-treated normal human B-lymphocyte populations. An antisense oligonucleotide complementary to the 5' coding region of the prohibitin gene blunted the increase in prohibitin protein in phorbol-ester-treated CLL B-cells by 42%. These data suggest that increased prohibitin expression is associated with and may facilitate B-cell maturation.
Woodlock
T J
TJ
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Bethlendy
G
G
Segel
G B
GB
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D000091402:Prohibitins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D010703:Phorbol Esters; D000091402:Prohibitins; D011506:Proteins; D012097:Repressor Proteins; D013755:Tetradecanoylphorbol Acetate