promyelocytic leukemia protein

The pathological hallmark of psoriasis is the infiltration of neutrophils into the skin. Some neutrophil-derived microRNAs (miRNAs) serve as biomarkers for various diseases, but none have been reported for psoriasis. Here, we investigated the involvement of miRNAs released from neutrophils in psoriasis pathogenesis. We compared the expression of miRNAs in the sera of patients with psoriasis and healthy individuals and found that the expression of two miRNAs, miR-223 and miR-1290, was significantly upregulated in the sera of patients with psoriasis...

The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy...

The formation and function of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, the maintenance of genome stability, responses to viral infection, apoptosis, and tumor suppression...

Acute promyelocytic leukemia (APL) is characterized by the fusion gene promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) and is conventionally treated with arsenic trioxide (ATO). ATO binds directly to the RING finger, B-box, coiled-coil (RBCC) domain of PML and initiates degradation of the fusion oncoprotein PML-RARA. However, the mutational hotspot at C212-S220 disrupts ATO binding, leading to drug resistance in APL. Therefore, structural consequences of these point mutations in PML that remain uncertain require comprehensive analysis...

The transcription factor promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16) is critical for the self-renewal of spermatogonial stem cells (SSCs). However, the function of PLZF in SSCs is not clear. Here, we found that PLZF acted as an epigenetic regulator of stem cell maintenance and self-renewal of germ cells. The PLZF protein interacts with the ten-eleven translocation 1 (TET1) protein and subsequently acts as a modulator to regulate the expression of self-renewal-related genes. Furthermore, Transcription Factor 7-like 2 (TCF7L2) is promoted by the coordination of PLZF and Tri-methylation of lysine 4 on histone H3 (H3K4me3)...

The genome is frequently targeted by genotoxic agents, resulting in the formation of DNA scars. However, cells employ diverse repair mechanisms to restore DNA integrity. Among these processes, the Mre11-Rad50-Nbs1 complex detects double-strand breaks (DSBs) and recruits DNA damage response proteins such as ataxia-telangiectasia-mutated (ATM) kinase to DNA damage sites. ATM phosphorylates the transactivation domain (TAD) of the p53 tumor suppressor, which in turn regulates DNA repair, growth arrest, apoptosis, and senescence following DNA damage...

Albeit N1-Methyladenosine (m1A) RNA modification represents an important regulator of RNA metabolism, the role of m1A modification in carcinogenesis remains enigmatic. Herein, we found that histone lactylation enhances ALKBH3 expression and simultaneously attenuates the formation of tumor-suppressive promyelocytic leukemia protein (PML) condensates by removing the m1A methylation of SP100A, promoting the malignant transformation of cancers. First, ALKBH3 is specifically upregulated in high-risk ocular melanoma due to excessive histone lactylation levels, referring to m1A hypomethylation status...

Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem/progenitor cells characterized by the abnormal proliferation of primitive and naive random cells in the bone marrow and peripheral blood. Acute promyelocytic leukemia (APL) is a type (AML-M3) of AML. Most patients with APL have the characteristic chromosomal translocation t(15; 17)(q22; q12), forming PML::RARA fusion. The occurrence and progression of AML are often accompanied by the emergence of gene fusions such as PML::RARA , CBFβ::MYH11 , and RUNX1::RUNX1T1 , among others...

Tripartite motif (TRIM)-containing proteins are a family of regulatory proteins that can participate in the induction of antiviral cytokines and antagonize viral replication. Promyelocytic leukemia (PML) protein is known as TRIM19 and is a major scaffold protein organizing the PML nuclear bodies (NBs). PML NBs are membrane-less organelles in the nucleus and play a diverse role in maintaining cellular homeostasis including antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV), a member virus of the family Arteriviridae, inhibits type I interferon (IFN) response during infection, and nonstructural protein 1 (nsp1) of the virus has been identified as a potent IFN antagonist...

BACKGROUND & OBJECTIVE: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to investigate the characteristics of Iranian APL patients, the distribution of PML-RARA isoforms, and survival analysis. METHODS: We included 145 consecutive eligible patients in this study...

The International Agency for Research on Cancer has unequivocally classified inorganic arsenic as a Group 1 carcinogen, definitively establishing its potential to induce cancer in humans. Paradoxically, despite its well-documented toxicity, arsenic finds utility as a chemotherapeutic agent. Notable examples include melarsoprol and arsenic trioxide, both employed in the treatment of acute promyelocytic leukemia. In both therapeutic and hazardous contexts, arsenic can accumulate within cellular environments, where it engages in intricate interactions with protein molecules...

UNLABELLED: The fate of herpesvirus genomes following entry into different cell types is thought to regulate the outcome of infection. For the Herpes simplex virus 1 (HSV-1), latent infection of neurons is characterized by association with repressive heterochromatin marked with Polycomb silencing-associated lysine 27 methylation on histone H3 (H3K27me). However, whether H3K27 methylation plays a role in repressing lytic gene expression in non-neuronal cells is unclear. To address this gap in knowledge, and with consideration that the fate of the viral genome and outcome of HSV-1 infection could be heterogeneous, we developed an assay to quantify the abundance of histone modifications within single viral genome foci of infected fibroblasts...

Arsenic trioxide (ATO) targets PML/RARα and leads to miraculous success in treating acute promyelocytic leukemia. Notably, ATO also targets p53, the most frequently mutated protein in cancers, through a similar binding mechanism. However, p53-targeting ATO trials are challenging due to the poor cellular uptake and cancer selectivity of ATO. Here, we analyzed the structure-activity relationship of arsenicals and rationally developed a novel arsenical (designated AcGlcAs) by conjugating arsenic to sulfur atoms and tetraacetyl-β-d-thioglucose...

PML bodies are subnuclear protein complexes that play a crucial role in various physiological and pathological cellular processes. One of the general structural proteins of PML bodies is a member of the tripartite motif (TRIM) family-promyelocytic leukemia protein (PML). It is known that PML interacts with over a hundred partners, and the protein itself is represented by several major isoforms, differing in their variable and disordered C-terminal end due to alternative splicing. Despite nearly 30 years of research, the mechanisms underlying PML body formation and the role of PML proteins in this process remain largely unclear...

BACKGROUND: Promyelocytic leukemia protein (PML) is a primary component of PML nuclear bodies (PML-NBs). PML and PML-NBs play critical roles in processes like the cell cycle, DNA damage repair, apoptosis, and the antiviral immune response. Previously, we identified five porcine PML alternative splicing variants and observed an increase in the expression of these PML isoforms following Japanese encephalitis virus (JEV) infection. In this study, we examined the functional roles of these PML isoforms in JEV infection...

Nuclear bodies (NBs) are biomolecular condensates that participate in various cellular processes and respond to cellular stimuli in the nucleus. The assembly and function of these protein- and RNA-rich bodies, such as nucleoli, nuclear speckles, and promyelocytic leukemia (PML) NBs, contribute to the spatial organization of the nucleus, regulating chromatin activities locally and globally. Recent technological advancements, including spatial multiomics approaches, have revealed novel roles of nucleoli in modulating ribosomal DNA (rDNA) and adjacent non-rDNA chromatin activity, nuclear speckles in scaffolding active genome architecture, and PML NBs in maintaining genome stability during stress conditions...

OBJECTIVES: Arsenic is one of the greatest hazards as an environmental carcinogen. At the same time it is also a promising anticancer agent, that can be used to treat acute promyelocytic leukemia (APL) and some other tumors. Arsenic trioxide (ATO) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells. However, the molecular mechanisms that govern these paradoxical effects of arsenic in bladder cancer remain unclear. We speculate that they share the common mechanism that arsenic binds to the target proteins and subsequently impacts the expression of downstream genes...

Promyelocytic leukemia (PML) protein constitutes an indispensable element within PML-nuclear bodies (PML-NBs), playing a pivotal role in the regulation of multiple cellular functions while coordinating the innate immune response against viral invasions. Simultaneously, numerous viruses elude immune detection by targeting PML-NBs. Japanese encephalitis virus (JEV) is a flavivirus that causes Japanese encephalitis, a severe neurological disease that affects humans and animals. However, the mechanism through which JEV evades immunity via PML-NBs has been scarcely investigated...

Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage. Comprehensive characterization of the mutants revealed that only the variant carrying four tryptophan substitutions per subunit retained the ability to disassemble and reassemble properly...

BACKGROUND: The anti-apoptotic protein B-Cell Lymphoma 2 (Bcl-2) is a key target for the development of anti-cancer agents, as its overexpression can render cancer cells resistant to chemotherapeutic treatments. AIMS AND OBJECTIVES: The current study has systematically evaluated a library of FDA-approved drugs for Bcl-2 inhibition using a drug repurposing strategy via in vitro, biophysical, and in-silico techniques. MATERIALS AND METHODS: In vitro anticancer activity was performed, followed by apoptosis assay...