scholarly journals Promyelocytic Leukemia Protein (Pml) and Daxx Participate in a Novel Nuclear Pathway for Apoptosis

2000 ◽  
Vol 191 (4) ◽  
pp. 631-640 ◽  
Author(s):  
Sue Zhong ◽  
Paolo Salomoni ◽  
Simona Ronchetti ◽  
Ailan Guo ◽  
Davide Ruggero ◽  
...  
Keyword(s):  
Acid Treatment ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Retinoic Acid Treatment ◽  
Promyelocytic Leukemia Protein ◽  
Disease Remission ◽  
Activation Induced Cell Death ◽  
A Cell ◽  
Dependent Pathway

The promyelocytic leukemia protein (PML) gene of acute promyelocytic leukemia (APL) encodes a cell growth and tumor suppressor essential for multiple apoptotic signals. Daxx was identified as a molecule important for the cytoplasmic transduction of the Fas proapoptotic stimulus. Here, we show that upon mitogenic activation of mature splenic lymphocytes, Daxx is dramatically upregulated and accumulates in the PML nuclear body (NB) where PML and Daxx physically interact. In the absence of PML, Daxx acquires a dispersed nuclear pattern, and activation-induced cell death of splenocytes is profoundly impaired. PML inactivation results in the complete abrogation of the Daxx proapoptotic ability. In APL cells, Daxx is delocalized from the NB. Upon retinoic acid treatment, which induces disease remission in APL, Daxx relocalizes to the PML NBs. These results indicate that PML and Daxx cooperate in a novel NB-dependent pathway for apoptosis and shed new light in the role of PML in tumor suppression.

scholarly journals C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation

2017 ◽  
Vol 130 (20) ◽  
pp. 3496-3506 ◽  
Author(s):  
Chuang Li ◽  
Qiongfang Peng ◽  
Xiao Wan ◽  
Haili Sun ◽  
Jun Tang
Keyword(s):  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Protein Isoforms ◽  
Promyelocytic Leukemia Protein ◽  
Body Formation

Acute Neutrophilic Dermatosis Induced by All-Trans-Retinoic Acid Treatment for Acute Promyelocytic Leukemia

1999 ◽  
Vol 34 (3-4) ◽  
pp. 401-404 ◽  
Author(s):  
Itai Levi ◽  
Pia Raanani ◽  
Bruria Shalmon ◽  
Regina Schiby-Brilliant ◽  
Isaac Ben-Bassat
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Acid Treatment ◽  
Promyelocytic Leukemia ◽  
Neutrophilic Dermatosis ◽  
Retinoic Acid Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Arkadia (RING Finger Protein 111) Mediates Sumoylation-Dependent Stabilization of Nrf2 Through K48-Linked Ubiquitination

2018 ◽  
Vol 46 (1) ◽  
pp. 418-430 ◽  
Author(s):  
Deneshia J. McIntosh ◽  
Treniqka S. Walters ◽  
Ifeanyi J. Arinze ◽  
Jamaine Davis
Keyword(s):  
Gene Transcription ◽  
Ring Finger ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Heme Oxygenase 1 ◽  
Ring Finger Protein ◽  
Whole Cell ◽  
Cell Lysates ◽  
Finger Protein

Background/Aims: The transcription factor Nrf2 is a master regulator of the antioxidant defense system, protecting cells from oxidative damage. We previously reported that the SUMO-targeted E3 ubiquitin ligase (STUbL), RING finger protein 4 (RNF4) accelerated the degradation rate of Nrf2 in promyelocytic leukemia-nuclear body (PML-NB)-enriched fractions and decreased Nrf2-mediated gene transcription. The mechanisms that regulate Nrf2 nuclear levels are poorly understood. In this study, we aim to explore the role of the second mammalian STUbL, Arkadia/RNF111 on Nrf2. Methods: Arkadia mediated ubiquitination was detected using co-immunoprecipitation assays in which whole cell lysates were immunoprecipated with anti-Nrf2 antibody and Western blotted with anti-hemagglutinin (HA) antibody or anti-Lys-48 ubiquitin-specific antibody. The half-life of Nrf2 was detected in whole cell lysates and promyelocytic leukemia-nuclear body enriched fractions by cycloheximide-chase. Reporter gene assays were performed using the antioxidant response element (ARE)-containing promoter Heme oxygenase-1 (HO-1). Results: We show that Arkadia/RNF111 is able to ubiquitinate Nrf2 resulting in the stabilization of Nrf2. This stabilization was mediated through Lys-48 ubiquitin chains, contrary to traditionally degradative role of Lys-48 ubiquitination, suggesting that Lys-48 ubiquitination of Nrf2 protects Nrf2 from degradation thereby allowing Nrf2-dependent gene transcription. Conclusion: Collectively, these findings highlight a novel mechanism to positively regulate nuclear Nrf2 levels in response to oxidative stress through Arkadia-mediated K48-linked ubiquitination of Nrf2.

scholarly journals A novel GTPase, CRAG, mediates promyelocytic leukemia protein–associated nuclear body formation and degradation of expanded polyglutamine protein

2006 ◽  
Vol 172 (4) ◽  
pp. 497-504 ◽  
Author(s):  
Qingyu Qin ◽  
Ryoko Inatome ◽  
Azusa Hotta ◽  
Masaki Kojima ◽  
Hirohei Yamamura ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Nuclear Body ◽  
Promyelocytic Leukemia ◽  
Dependent Manner ◽  
Polyglutamine Diseases ◽  
Promyelocytic Leukemia Protein ◽  
Localization Signal ◽  
Guanosine Triphosphatase ◽  
Interfering Rna ◽  
Polyglutamine Protein

Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG–polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin–proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases.

All-Trans-Retinoic Acid Treatment for Patients with Acute Promyelocytic Leukemia

2015 ◽  
pp. 121-126
Author(s):  
L. Degos ◽  
C. Chomienne ◽  
M. T. Daniel ◽  
R. Berger ◽  
S. Castaigne
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Acid Treatment ◽  
Promyelocytic Leukemia ◽  
Retinoic Acid Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Successful all-trans retinoic acid treatment of acute promyelocytic leukemia in a patient with NPM/RAR fusion

2007 ◽  
Vol 86 (3) ◽  
pp. 246-249 ◽  
Author(s):  
Kiyoshi Okazuka ◽  
Masayoshi Masuko ◽  
Yoshinobu Seki ◽  
Hitomi Hama ◽  
Noriyuki Honma ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Acid Treatment ◽  
Promyelocytic Leukemia ◽  
Retinoic Acid Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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