Lysine Deacetylation Is a Key Function of the Lysyl Oxidase Family of Proteins in Cancer.

Mammalian members of the lysyl oxidase (LOX) family of proteins carry a copper-dependent monoamine oxidase domain exclusively within the C-terminal region, which catalyzes ε-amine oxidation of lysine residues of various proteins. However, recent studies have demonstrated that in LOX-like (LOXL) 2-4 the C-terminal canonical catalytic domain and N-terminal scavenger receptor cysteine-rich (SRCR) repeats domain exhibit lysine deacetylation and deacetylimination catalytic activities. Moreover, the N-terminal SRCR repeats domain is more catalytically active than the C-terminal oxidase domain.

Irisin deficiency exacerbates diet-induced insulin resistance and cardiac dysfunction in type II diabetes in mice.

Irisin is involved in the regulation of a variety of physiological conditions, metabolism, and survival. We and others have demonstrated that irisin contributes critically to modulation of insulin resistance and the improvement of cardiac function. However, whether the deletion of irisin will regulate cardiac function and insulin sensitivity in type II diabetes remains unclear.

Inhibition of integrin alpha v/beta 5 mitigates the protective effect induced by irisin in hemorrhage.

Introduction: Irisin plays an important role in regulating tissue stress, cardiac function, and inflammation. Integrin αvβ5 was recently identified as a receptor for irisin to elicit its physiologic function. It remains unknown whether integrin αvβ5 is required for irisin's function in modulating the physiologic response to hemorrhage.

Protein Kinase C Modulation Determines the Mesoderm/Extraembryonic Fate Under BMP4 Induction From Human Pluripotent Stem Cells.

The interplay among mitogenic signaling pathways is crucial for proper embryogenesis. These pathways collaboratively act through intracellular master regulators to determine specific cell fates. Identifying the master regulators is critical to understanding embryogenesis and to developing new applications of pluripotent stem cells.

NF-κB represses retinoic acid receptor-mediated GPRC5A transactivation in lung epithelial cells to promote neoplasia.

Chronic inflammation is associated with lung tumorigenesis, in which NF-κB-mediated epigenetic regulation plays a critical role. Lung tumor suppressor G protein-coupled receptor, family C, member 5A (GPRC5A), is repressed in most non-small cell lung cancer (NSCLC); however, the mechanisms remain unclear. Here, we show that NF-κB acts as a transcriptional repressor in suppression of GPRC5A.

Anti-tumour potential of PD-L1/PD-1 post-translational modifications.

The immune checkpoint programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) are biologically important immunosuppressive molecules, and the PD-L1/PD-1-mediated signalling pathway is currently considered one of the main mechanisms of tumour escape immune surveillance. PD-L1 is highly expressed on the cytomembrane of tumour cell and binds to PD-1 receptor of activated T cells. This interaction activates PD-L1/PD-1 downstream signal transduction, inhibiting T cells anti-tumour activity.

Identification of Immune-Related Gene Signature and Prediction of CeRNA Network in Active Ulcerative Colitis.

Background: Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and its incidence is steadily increasing worldwide. Intestinal immune dysfunction has been identified as a central event in UC pathogenesis. However, the underlying mechanisms that regulate dysfunctional immune cells and inflammatory phenotype remain to be fully elucidated.

S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome.

In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane-bound transcription factor peptidase/site-1 protease (MBTPS1, S1P).

Identification of Active Bronchioalveolar Stem Cells as the Cell of Origin in Lung Adenocarcinoma.

Unlabelled: While initiation is established as a critical step in tumorigenesis, the identity of the cell of origin for lung adenocarcinoma and the mechanism controlling susceptibility to initiation remain elusive. Here we show that lung tumor suppressor Gprc5a-knockout (KO) mice are susceptible to initiation of lung tumorigenesis. Bronchioalveolar stem cells (BASC) and alveolar type 2 (AT2) cells were aberrantly expanded in Gprc5a-KO mouse lungs compared with those in wild-type (WT) mice, suggesting that Gprc5a-KO might confer susceptibility to initiation by increasing the cell of origin in mouse lungs.

Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.

The mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive.

Roles of Mitochondrial Serine Hydroxymethyltransferase 2 (SHMT2) in Human Carcinogenesis.

In the last few years, cellular metabolic reprogramming has been acknowledged as a hallmark of human cancer and evaluated for its crucial role in supporting the proliferation and survival of human cancer cells. In a variety of human tumours, including hepatocellular carcinoma (HCC), breast cancer and non-small-cell lung cancer (NSCLC), a large amount of carbon is reused in serine/glycine biosynthesis, accompanied by higher expression of the key glycine synthetic enzyme mitochondrial serine hydroxymethyltransferase 2 (SHMT2). This enzyme can convert serine into glycine and a tetrahydrofolate-bound one-carbon unit, ultimately supporting thymidine synthesis and purine synthesis and promoting tumour growth.

Emerging role of SIRT2 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most devastating cancer types, accounting for >80% of lung cancer cases. The median relative survival time of patients with NSCLC is <1 year. Lysine acetylation is a major post-translational modification that is required for various biological processes, and abnormal protein acetylation is associated with various diseases, including NSCLC.

The Essential Role of PRAK in Preserving Cardiac Function and Insulin Resistance in High-Fat Diet-Induced Diabetes.

Regulated/activated protein kinase (PRAK) plays a crucial role in modulating biological function. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high-fat diet (HFD).

Furin Enzyme and pH Synergistically Triggered Aggregation of Gold Nanoparticles for Activated Photoacoustic Imaging and Photothermal Therapy of Tumors.

Specific and effective accumulation of nanoparticles within tumors is highly crucial for precise cancer diagnosis and treatment. Therefore, spatiotemporally manipulating the aggregation of small gold nanoparticles (AuNPs) in a tumor microenvironment is of great significance for enhancing the diagnostic and therapeutic efficacy of tumors. Herein, we reported a novel furin enzyme/acidic pH synergistically triggered small AuNP aggregation strategy for activating the photoacoustic (PA) imaging and photothermal (PTT) functions of AuNPs in vivo.

Myristoylation-mediated phase separation of EZH2 compartmentalizes STAT3 to promote lung cancer growth.

N-myristoylation is a crucial signaling and pathogenic modification process that confers hydrophobicity to cytosolic proteins. Although different large-scale approaches have been applied, a large proportion of myristoylated proteins remain to be identified. EZH2 is overexpressed in lung cancer cells and exerts oncogenic effects via its intrinsic methyltransferase activity.

SQR mediates therapeutic effects of HS by targeting mitochondrial electron transport to induce mitochondrial uncoupling.

Hydrogen sulfide (HS) is a gasotransmitter and a potential therapeutic agent. However, molecular targets relevant to its therapeutic actions remain enigmatic. Sulfide-quinone oxidoreductase (SQR) irreversibly oxidizes HS.

LOXL1 modulates the malignant progression of colorectal cancer by inhibiting the transcriptional activity of YAP.

Background: LOX-like 1 (LOXL1) is a lysyl oxidase, and emerging evidence has revealed its effect on malignant cancer progression. However, its role in colorectal cancer (CRC) and the underlying molecular mechanisms have not yet been elucidated.

Methods: LOXL1 expression in colorectal cancer was detected by immunohistochemistry, western blotting and real-time PCR.

Irisin Improves Myocardial Performance and Attenuates Insulin Resistance in Spontaneous Mutation ( ) Mice.

Background: Irisin, a newly identified peptide, is critical to regulating metabolism, thermogenesis, and reducing oxidative stresses. Our recent works demonstrated that irisin protected the heart against myocardial ischemic injury and preserved the function of mitochondria. However, whether irisin preserves myocardial performance and attenuates insulin resistance in type II diabetes remains unknown.

Senescent Stromal Cells Promote Cancer Resistance through SIRT1 Loss-Potentiated Overproduction of Small Extracellular Vesicles.

Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype, which is implicated in age-related pathologies including cancer. Here, we report that senescent cells actively synthesize and release small extracellular vesicles (sEV) with a distinctive size distribution.