scholarly journals Control of Hepatic Gluconeogenesis by the Promyelocytic Leukemia Zinc Finger Protein

2014 ◽  
Vol 28 (12) ◽  
pp. 1987-1998 ◽  
Author(s):  
Siyu Chen ◽  
Jinchun Qian ◽  
Xiaoli Shi ◽  
Tingting Gao ◽  
Tingming Liang ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Metabolic Diseases ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Peroxisome Proliferator ◽  
Hepatic Gluconeogenesis ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Glucose ◽  
Glucose Output

The promyelocytic leukemia zinc finger (PLZF) protein is involved in major biological processes including energy metabolism, although its role remains unknown. In this study, we demonstrated that hepatic PLZF expression was induced in fasted or diabetic mice. PLZF promoted gluconeogenic gene expression and hepatic glucose output, leading to hyperglycemia. In contrast, hepatic PLZF knockdown improved glucose homeostasis in db/db mice. Mechanistically, peroxisome proliferator-activated receptor γ coactivator 1α and the glucocorticoid receptor synergistically activated PLZF expression. We conclude that PLZF is a critical regulator of hepatic gluconeogenesis. PLZF manipulation may benefit the treatment of metabolic diseases associated with gluconeogenesis.

scholarly journals Promyelocytic Leukemia Zinc Finger Protein Regulates Interferon-Mediated Innate Immunity

Immunity ◽  
2009 ◽  
Vol 30 (6) ◽  
pp. 802-816 ◽  
Author(s):  
Dakang Xu ◽  
Michelle Holko ◽  
Anthony J. Sadler ◽  
Bernadette Scott ◽  
Shigeki Higashiyama ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Finger Protein

AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3939-3947 ◽  
Author(s):  
Ari Melnick ◽  
Graeme W. Carlile ◽  
Melanie J. McConnell ◽  
Adam Polinger ◽  
Scott W. Hiebert ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Zinc Finger ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Dominant Negative ◽  
Myelogenous Leukemia ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Dominant Negative Inhibitor

Abstract The AML-1/ETO fusion protein, created by the (8;21) translocation in M2-type acute myelogenous leukemia (AML), is a dominant repressive form of AML-1. This effect is due to the ability of the ETO portion of the protein to recruit co-repressors to promoters of AML-1 target genes. The t(11;17)(q21;q23)-associated acute promyelocytic leukemia creates the promyelocytic leukemia zinc finger PLZFt/RARα fusion protein and, in a similar manner, inhibits RARα target gene expression and myeloid differentiation. PLZF is expressed in hematopoietic progenitors and functions as a growth suppressor by repressing cyclin A2 and other targets. ETO is a corepressor for PLZF and potentiates transcriptional repression by linking PLZF to a histone deacetylase-containing complex. In transiently transfected cells and in a cell line derived from a patient with t(8;21) leukemia, PLZF and AML-1/ETO formed a tight complex. In transient assays, AML-1/ETO blocked transcriptional repression by PLZF, even at substoichiometric levels relative to PLZF. This effect was dependent on the presence of the ETO zinc finger domain, which recruits corepressors, and could not be rescued by overexpression of co-repressors that normally enhance PLZF repression. AML-1/ETO also excluded PLZF from the nuclear matrix and reduced its ability to bind to its cognate DNA-binding site. Finally, ETO interacted with PLZF/RARα and enhanced its ability to repress through the RARE. These data show a link in the transcriptional pathways of M2 and M3 leukemia.

scholarly journals The GTPase domain of Galphao contributes to the functional interaction of Galphao with the promyelocytic leukemia zinc finger protein

2009 ◽  
Vol 14 (1) ◽  
Author(s):  
Jung Won ◽  
Sung Ghil
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Functional Interaction ◽  
Gtpase Domain ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Downstream Effector ◽  
Finger Protein ◽  
Family Based ◽  
G Protein Coupled

AbstractGo, one of the most abundant heterotrimeric G proteins in the brain, is classified as a member of the Gi/Go family based on its homology to Gi proteins. Recently, we identified promyelocytic leukemia zinc finger protein (PLZF) as a candidate downstream effector for the alpha subunit of Go (Gαo). Activated Gαo interacts with PLZF and augments its function as a repressor of transcription and cell growth. G protein-coupled receptor-mediated Gαo activation also enhanced PLZF function. In this study, we determined that the GTPase domain of Gαo contributes to Gαo:PLZF interaction. We also showed that the Gαo GTPase domain is important in modulating the function of PLZF. This data indicates that the GTPase domain of Gαo may be necessary for the functional interaction of Gαo with PLZF.

scholarly journals Sequence-specific DNA Binding and Transcriptional Regulation by the Promyelocytic Leukemia Zinc Finger Protein

1997 ◽  
Vol 272 (36) ◽  
pp. 22447-22455 ◽  
Author(s):  
Jia-Yuan Li ◽  
Milton A. English ◽  
Helen J. Ball ◽  
Patricia L. Yeyati ◽  
Samuel Waxman ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Finger Protein

scholarly journals The Promyelocytic Leukemia Zinc Finger Protein Affects Myeloid Cell Growth, Differentiation, and Apoptosis

1998 ◽  
Vol 18 (9) ◽  
pp. 5533-5545 ◽  
Author(s):  
Rita Shaknovich ◽  
Patricia L. Yeyati ◽  
Sarah Ivins ◽  
Ari Melnick ◽  
Cheryl Lempert ◽  
...  
Keyword(s):  
Cell Growth ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Myeloid Cell ◽  
Suppressive Effect ◽  
Promyelocytic Leukemia ◽  
Critical Event ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Myeloid Development ◽  
Macrophage Colony

ABSTRACT The promyelocytic leukemia zinc finger (PLZF) gene, which is disrupted in therapy-resistant, t(11;17)(q23;q21)-associated acute promyelocytic leukemia (APL), is expressed in immature hematopoietic cells and is down-regulated during differentiation. To determine the role of PLZF in myeloid development, we engineered expression of PLZF in murine 32Dcl3 cells. Expression of PLZF had a dramatic growth-suppressive effect accompanied by accumulation of cells in the G0/G1 compartment of the cell cycle and an increased incidence of apoptosis. PLZF-expressing pools also secreted a growth-inhibitory factor, which could explain the severe growth suppression of PLZF-expressing pools that occurred despite the fact that only half of the cells expressed high levels of PLZF. PLZF overexpression inhibited myeloid differentiation of 32Dcl3 cells in response to granulocyte and granulocyte-macrophage colony-stimulating factors. Furthermore, cells that expressed PLZF appeared immature as demonstrated by morphology, increased expression of Sca-1, and decreased expression of Gr-1. These findings suggest that PLZF is an important regulator of cell growth, death, and differentiation. Disruption of PLZF function associated with t(11;17) may be a critical event leading to APL.

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