Tp73

Polyamines promote cellular proliferation. Their levels are controlled by ornithine decarboxylase antizyme 1 (Az1, encoded by OAZ1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az1-mediated degradation of other substrates such as cyclin D1 (CCND1), DNp73 (TP73) or Mps1 regulates cell growth and centrosome amplification, and the currently known six Az1 substrates are all linked with tumorigenesis. To understand whether Az1-mediated protein degradation might play a role in regulating other cellular processes associated with tumorigenesis, we employed quantitative proteomics to identify novel Az1 substrates...

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BACKGROUND: The ubiquitin protein ligase E3C (UBE3C) has been reported to play an oncogenic role in breast cancer (BRCA). This work further investigates the effect of UBE3C on the radioresistance of BRCA cells. METHODS: Molecules linking to radioresistance in BRCA were identified by analyzing two GEO datasets, GSE31863 and GSE101920. UBE3C overexpression or knockdown was induced in parental or radioresistant BRCA cells, followed by irradiation treatment. The malignant properties of cells in vitro, and the growth and metastatic activity of cells in nude mice, were analyzed...

OBJECTIVE: The present study opted for the adrenal phaeochromocytoma (PC12) cell line to frame a neuronal injury model induced by alcohol exposure in vitro, aiming to probe whether TAp73 and miR-96-5p are involved in the neuronal injury process induced by alcohol and elucidate the regulatory relationship between miR-96-5p and TAp73. METHODS: Immunofluorescence staining was used to observe the structural features of PC12 cells after culturing in medium with nerve growth factor (NGF)...

We aimed to identify the immune and Toll-like receptor (TLR) signaling pathway related feature lncRNAs to construct the diagnostic nomograms for acute ischemic stroke (AIS). Two AIS-associated expression profiles GSE16561 and GSE22255 were downloaded from NCBI Gene Expression Omnibus, the former was the training set and the latter was the validation set. The differential expression genes (DEGs) and lncRNAs (DElncRNAs) related to TLR signaling pathway were identified between AIS and control groups. The single sample gene set enrichment analysis (ssGSEA) was applied to evaluate the immune infiltration...

INTRODUCTION: The bone matrix protein osteocalcin (OC), secreted by osteoblasts, displays endocrine effects. We tested the hypothesis that OC modulates parathyroid tumor cell function. METHODS: Primary cell cultures derived from parathyroid adenomas (PAds) and HEK293 cells transiently transfected with the putative OC receptor GPRC6A or the calcium sensing receptor (CASR) were used as experimental models to investigate γ-carboxylated OC (GlaOC) or uncarboxylated OC (GluOC) modulation of intracellular signaling...

The microtubule-targeting paclitaxel (PTX) and docetaxel (DTX) are widely used chemotherapeutic agents. However, the dysregulation of apoptotic processes, microtubule-binding proteins, and multi-drug resistance efflux and influx proteins can alter the efficacy of taxane drugs. In this review, we have created multi-CpG linear regression models to predict the activities of PTX and DTX drugs through the integration of publicly available pharmacological and genome-wide molecular profiling datasets generated using hundreds of cancer cell lines of diverse tissue of origin...

Tumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses, such as Epstein-Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis. To gain additional insight into ΔNp73α mechanisms, we have performed proteomics analyses using human keratinocytes transformed by the E6 and E7 proteins of the beta-HPV type 38 virus as an experimental model (38HK)...

OBJECTIVE: TP73-AS1 can promote the occurrence and development of a variety of tumors, including colorectal cancer (CRC). The current study aimed to investigate the association between a potentially functional genetic polymorphism (rs3737589 T > C) on the TP73-AS1 gene and the susceptibility and clinical stage of CRC in a Chinese Han population. METHODS: The polymorphic genotyping was performed by the SNaPshot method. The real-time quantitative PCR method and the luciferase assay were used separately to explore genotype-tissue expression and the function of the genetic polymorphism...

INTRODUCTION: TP73 was recently identified as a novel causative gene for amyotrophic lateral sclerosis (ALS). We aimed to determine the contribution of variations in TP73 in the Chinese ALS population and to further explore the genotype-phenotype correlations. METHODS: We screened rare, putative pathogenic TP73 mutations in a large Chinese ALS cohort and performed association analysis of both rare and common TP73 variations between cases and controls. RESULTS: Of the 985 ALS patients studied, six rare, heterozygous putative pathogenic variants in TP73 were identified among six unrelated sALS patients...

Peptides/small proteins, encoded by noncanonical open reading frames (ORF) of previously claimed non-coding RNAs, have recently been recognized possessing important biological functions, but largely uncharacterized. 1p36 is an important tumor suppressor gene (TSG) locus frequently deleted in multiple cancers, with critical TSGs like TP73, PRDM16, and CHD5 already validated. Our CpG methylome analysis identified a silenced 1p36.3 gene KIAA0495, previously thought coding long non-coding RNA. We found that the open reading frame 2 of KIAA0495 is actually protein-coding and translating, encoding a small protein SP0495...

Epstein-Barr virus (EBV) is one of the major drivers of gastric carcinogenesis. EBV infection is established before tumour initiation and is generally maintained throughout tumour development; however, the significance of EBV in tumour maintenance and progression remains to be elucidated. Here, we report eight cases of EBV-associated gastric carcinoma (EBVaGC) with intratumoural heterogenous expression of EBV-encoded small RNA (EBER), a highly expressed latent gene of EBV, and demonstrate clinicopathologic characteristics of these rare cases...

Colorectal cancer (CC) is one of the most aggressive cancers, with a high mortality rate worldwide. This study focuses on the mechanism of CC to explore the effective therapeutic targets. We determined that LncRNA TP73-AS1 (TP-73-AS1) expression was significantly increased in CC tissues. TP73-AS1 silencing dynamically inhibited the proliferation, migratory and invasive capacity in CC cells. Mechanistically, we found that TP73-AS1 targeted miR-539-5p and miR-539-5p silencing could promote the migratory and invasive capacity in CC cells...

Deregulation of Pol III products causes a range of diseases, including neural diseases and cancers. However, the factors and mechanisms that modulate Pol III-directed transcription remain to be found, although massive advances have been achieved. Here, we show that STAT3 positively regulates the activities of Pol III-dependent transcription and cancer cell growth. RNA-seq analysis revealed that STAT3 inhibits the expression of TP73, a member of the p53 family. We found that TP73 is not only required for the regulation of Pol III-directed transcription mediated by STAT3 but also independently suppresses the synthesis of Pol III products...

TP73 is expressed as multiple N- and C-terminal isoforms through two separate promoters or alternative splicing. While N-terminal p73 isoforms have been well studied, very little is known about p73 C-terminal isoforms. Thus, CRISPR was used to delete TP73 Exon13 (E13-KO) to induce p73α to p73β isoform switch. We showed that E13-KO led to decreased cell proliferation and migration and sensitized cells to ferroptosis, which can be reverted by knockdown of TAp73β in E13-KO cells. To understand the biological function of p73β in vivo, we generated a mouse model in that the Trp73 E13 was deleted by CRISPR...

Metastatic melanoma is one of the most aggressive tumors, with frequent mutations affecting components of the MAPK pathway, mainly protein kinase BRAF. Despite promising initial response to BRAF inhibitors, melanoma progresses due to development of resistance. In addition to frequent reactivation of MAPK or activation of PI3K/AKT signaling pathways, recently, the p53 pathway has been shown to contribute to acquired resistance to targeted MAPK inhibitor therapy. Canonical tumor suppressor p53 is inactivated in melanoma by diverse mechanisms...

TP53 (TP53), p73 (TP73), and p63 (TP63) are members of the p53 transcription factor family, which has many activities spanning from embryonic development through to tumor suppression. The utilization of two promoters and alternative mRNA splicing has been shown to yield numerous isoforms in p53, p63, and p73. TAp73 is thought to mediate apoptosis as a result of nuclear accumulation following chemotherapy-induced DNA damage, according to a number of studies. Overexpression of the nuclear ΔNp63 and ΔNp73 isoforms, on the other hand, suppresses TAp73's pro-apoptotic activity in human malignancies, potentially leading to metastatic spread or inhibition...

Drug resistance is a major obstacle to the successful treatment of cancer. The role of the miR-106b-25 cluster in drug resistance of haematologic malignancies has not yet been elucidated. Here, we show that the miR-106b-25 cluster mediates resistance to therapeutic agents with structural and mechanistic dissimilarity in vitro and in vivo. RNA sequencing data revealed that overexpression of the miR-106b-25 cluster or its individual miRNAs resulted in downregulation of multiple key regulators of apoptotic pathways...

The histone methyltransferase SET domain-containing protein 8 (SETD8), which methylates histone H4 lysine 20 (H4K20) and non-histone proteins such as p53, plays key roles in human carcinogenesis. Our aim was to determine the involvement of SETD8 in endometrial cancer and its therapeutic potential and identify the downstream genes regulated by SETD8 via H4K20 methylation and the p53 signaling pathway. We examined the expression profile of SETD8 and evaluated whether SETD8 plays a critical role in the proliferation of endometrial cancer cells using small interfering RNAs (siRNAs)...