DCUN1D1 and neddylation: Potential targets for cancer therapy.

Cancer affects millions of people and understanding the molecular mechanisms related to disease development and progression is essential to manage the disease. Post-translational modification (PTM) processes such as ubiquitination and neddylation have a significant role in cancer development and progression by regulating protein stability, function, and interaction with other biomolecules. Both ubiquitination and neddylation are analogous processes that involves a series of enzymatic steps leading to the covalent attachment of ubiquitin or NEDD8 to target proteins.

Transcription Factors in Prostate Cancer: Insights for Disease Development and Diagnostic and Therapeutic Approaches.

Transcription factors (TFs) are proteins essential for the regulation of gene expression, and they regulate the genes involved in different cellular processes, such as proliferation, differentiation, survival, and apoptosis. Although their expression is essential in normal physiological conditions, abnormal regulation of TFs plays critical role in several diseases, including cancer. In prostate cancer, the most common malignancy in men, TFs are known to play crucial roles in the initiation, progression, and resistance to therapy of the disease.

The influence of a copper efflux pump in Histoplasma capsulatum virulence.

During the infectious process, pathogenic microorganisms must obtain nutrients from the host in order to survive and proliferate. These nutritional sources include the metallic nutrient copper. Despite its essentiality, copper in large amounts is toxic.

DCUN1D1 Is an Essential Regulator of Prostate Cancer Proliferation and Tumour Growth That Acts through Neddylation of Cullin 1, 3, 4A and 5 and Deregulation of Wnt/Catenin Pathway.

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previously explored thoroughly. Here, we investigated the role of DCUN1D1 in PCa and demonstrated that DCUN1D1 is upregulated in cell lines as well as human tissue samples.

Formamidase Contributes to Fungal Survival in Macrophages.

Nitrogen is a crucial nutrient for microorganisms that compose essential biomolecules. However, hosts limit this nutrient as a strategy to counter infections, therefore, pathogens use adaptive mechanisms to uptake nitrogen from alternative sources. In fungi, nitrogen catabolite repression (NCR) activates transcription factors to acquire nitrogen from alternative sources when preferential sources are absent.

Iron Deprivation Modulates the Exoproteome in .

Fungi of the genus are the etiological agents of the systemic mycosis paracoccidioidomycosis and, when in the host, they find a challenging environment that is scarce in nutrients and micronutrients, such as Fe, which is indispensable for the survival of the pathogen. Previous studies have shown that fungi of this genus, in response to Fe deprivation, are able to synthesize and capture siderophores (Fe chelators), use Fe-containing host proteins as a source of the metal, and use a non-canonical reductive pathway for Fe assimilation. Despite all of these findings, there are still gaps that need to be filled in the pathogen response to metal deprivation.

Challenges in Serologic Diagnostics of Neglected Human Systemic Mycoses: An Overview on Characterization of New Targets.

Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. However, the diagnosis of fungal infections represents a great challenge because of the decline in the expertise needed for identifying fungi, and a reduced number of instruments and assays specific to fungal identification.

The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications.

Resistance to chemotherapeutic agents by cancer cells has remained a major obstacle in the successful treatment of various cancers. Numerous factors such as DNA damage repair, cell death inhibition, epithelial-mesenchymal transition, and evasion of apoptosis have all been implicated in the promotion of chemoresistance. The receptor tyrosine kinase Axl, a member of the TAM family (which includes TYRO3 and MER), plays an important role in the regulation of cellular processes such as proliferation, motility, survival, and immunologic response.

Interacting with Hemoglobin: spp. Recruits hsp30 on Its Cell Surface for Enhanced Ability to Use This Iron Source.

spp. are thermally dimorphic fungi that cause paracoccidioidomycosis and can affect both immunocompetent and immunocompromised individuals. The infection can lead to moderate or severe illness and death.

Metabolic Adaptation of in Response to Copper Deprivation.

Copper is an essential micronutrient for the performance of important biochemical processes such as respiration detoxification, and uptake of metals like iron. Studies have shown that copper deprivation is a strategy used by the host against pathogenic fungi such as and during growth and development of infections in the lungs and kidneys. Although there are some studies, little is known about the impact of copper deprivation in members of the genus.

Nitrogen Catabolite Repression in members of Paracoccidioides complex.

Paracoccidioides complex is a genus that comprises pathogenic fungi which are responsible by systemic disease Paracoccidioidomycosis. In host tissues, pathogenic fungi need to acquire nutrients in order to survive, making the uptake of nitrogen essential for their establishment and dissemination. Nitrogen utilization is employed by the alleviation of Nitrogen Catabolite Repression (NCR) which ensures the use of non-preferential or alternative nitrogen sources when preferential sources are not available.

Immunoproteomic Approach of Extracellular Antigens From Species Reveals Exclusive B-Cell Epitopes.

Fungi of the genus are the etiological agents of paracoccidioidomycosis (PCM), a systemic mycosis restricted to the countries of Latin America. Currently, the complex is represented by , , , , and . Even with advances in techniques used for diagnosing fungal diseases, high rates of false-positive results for PCM are still presented.

Proteomic Analyses Elucidate Differences in the Protein Repertories among Clinical Strains Related to Virulence and Persistence.

is a Gram-positive and coagulase negative cocci that composes the skin microbiota and can act as an opportunistic agent causing urinary tract infections, being more frequent in sexually active young women. The ability of a pathogen to cause infection in the host is associated to its ability to adhere to host cells and to survive host immune defenses. In this work, we presented the comparative proteomic profile of three strains.

The influence of pH on Staphylococcus saprophyticus iron metabolism and the production of siderophores.

Staphylococcus saprophyticus is a gram-positive coagulase negative bacteria which shows clinical importance due to its capability of causing urinary tract infections (UTI), as well as its ability to persist in this environment. Little is known about how S. saprophyticus adapts to the pH shift that occurs during infection.

Identification and characterization of Paracoccidioides lutzii proteins interacting with macrophages.

Paracoccidioidomycosis (PCM), caused by thermodimorphic fungi of the Paracoccidioides genus, is a systemic disorder that involves the lungs and other organs. The adherence of pathogenic microorganisms to host tissues is an essential event in the onset of colonization and spread. The host-pathogen interaction is a complex interplay between the defense mechanisms of the host and the efforts of pathogenic microorganisms to colonize it.

Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl.

Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells.

In silico characterization of microRNAs-like sequences in the genome of Paracoccidioides brasiliensis.

Eukaryotic cells have different mechanisms of post-transcriptional regulation. Among these mechanisms, microRNAs promote regulation of targets by cleavage or degradation of the mRNA. Fungi of the Paracoccidioides complex are the etiological agents of the main systemic mycosis of Latin America.

Cell Wall Synthesis, Development of Hyphae and Metabolic Pathways Are Processes Potentially Regulated by MicroRNAs Produced Between the Morphological Stages of .

MicroRNAs are molecules involved in post-transcriptional gene regulation. In pathogenic fungi, microRNAs have been described at different morphological stages by regulating targets involved in processes such as morphogenesis and energy production. Members of the complex are the main etiological agents of a systemic mycosis in Latin America.

The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview.

Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers.

In vitro, ex vivo and in vivo models: A comparative analysis of Paracoccidioides spp. proteomic studies.

Members of the Paracoccidioides complex are human pathogens that infect different anatomic sites in the host. The ability of Paracoccidioides spp. to infect host niches is putatively supported by a wide range of virulence factors, as well as fitness attributes that may comprise the transition from mycelia/conidia to yeast cells, response to deprivation of micronutrients in the host, expression of adhesins on the cell surface, response to oxidative and nitrosative stresses, as well as the secretion of hydrolytic enzymes in the host tissue.

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi.

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses.

Potential role of P2X7R in esophageal squamous cell carcinoma proliferation.

Esophageal cancer is an aggressive tumor and is the sixth leading cause of cancer death worldwide. ATP is well known to regulate cancer progression in a variety of models by different mechanisms, including P2X7R activation. This study aimed to evaluate the role of P2X7R in esophageal squamous cell carcinoma (ESCC) proliferation.

GADD45α and γ interaction with CDK11p58 regulates SPDEF protein stability and SPDEF-mediated effects on cancer cell migration.

The epithelium-specific Ets transcription factor, SPDEF, plays a critical role in metastasis of prostate and breast cancer cells. While enhanced SPDEF expression blocks migration and invasion, knockdown of SPDEF expression enhances migration, invasion, and metastasis of cancer cells. SPDEF expression and activation is tightly regulated in cancer cells; however, the precise mechanism of SPDEF regulation has not been explored in detail.

Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells.

Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform.