The promyelocytic leukemia zinc finger protein down-regulates apoptosis and expression of the proapoptotic BID protein in lymphocytes.
The promyelocytic leukemia zinc finger (PLZF) gene, involved in rare cases of acute promyelocytic leukemia, encodes a Krüppel-type zinc finger transcription factor. It has been reported that PLZF affects myeloid cell growth, differentiation, and apoptosis. However, the function of PLZF in the lymphoid compartment, where PLZF is also expressed, remains largely unknown. To investigate a potential relationship between PLZF expression in lymphocytes and programmed cell death, an inducible model of stable clones of the lymphoid Jurkat cell line was created by using the tet-off system. Although induction of PLZF expression by itself did not produce changes in the basal levels of apoptosis, PLZF had a significant anti-apoptotic effect in Jurkat cells cultured in conditions of serum starvation, as measured by annexin V staining and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. In addition, retarded loss of mitochondrial transmembrane potential was observed in the PLZF-expressing clones, suggesting that PLZF protects from cell death through a mitochondrial-dependent mechanism. To identify apoptosis-related targets of PLZF, a screen for differential expression identified BID, a proapoptotic member of the Bcl2 family, as significantly down-regulated by PLZF. Furthermore, a high-affinity PLZF-binding site element was identified upstream of the BID transcriptional start site, as assessed by electrophoretic mobility-shift assays. These results suggest that BID is a target of PLZF repression and a candidate gene to mediate the PLZF-induced resistance to apoptosis.
Parrado
Antonio
A
Servicio de Inmunología, Hospital Universitario Virgen de la Arrixaca, 31020 Murcia, Spain. antonio.parrado@carm.es
Robledo
Macarena
M
Moya-Quiles
M Rosa
MR
Marín
Luis A
LA
Chomienne
Christine
C
Padua
Rose Ann
RA
Alvarez-López
M Rocío
MR
D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000235:genetics*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D051741:Kruppel-Like Transcription Factors; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D008564:Membrane Potentials; D011401:Promoter Regions, Genetic / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014157:Transcription Factors; C092037:ZBTB16 protein, human