PAWR (PRKC apoptosis WT1 regulator protein; Prostate apoptosis response-4, Par-4)

Review on PAWR, with data on DNA, on the protein encoded, and where the gene is implicated

A Naturally Generated Decoy of the Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance in Tumors

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA segment, competitively bound to Fbxo45 and rescued Par-4–mediated induction of cancer cell–specific apoptosis. Collectively, our findings identify a molecular decoy naturally generated during apoptosis that inhibits a ubiquitin ligase to overcome therapy resistance in tumors

Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings indicate that CQ induces p53- and Rab8b-dependent Par-4 secretion from normal cells for Par-4-dependent inhibition of metastatic tumor growth

The prevalence of early childhood caries and treatment needs among children attending Anganwadi centers in Goa state: A cross-sectional survey

Context: The prevalence of early childhood caries (ECC) is widespread, as reported in studies conducted in various states across India. Many children residing in the rural areas attend Anganwadi centers for preprimary education, nourishment, and health care. Aim: The aim of the study was to determine the prevalence of ECC among children attending Anganwadi centers in the state of Goa and their treatment needs. Settings and Design: The study was approved by the Institutional Ethical Committee of Goa Dental College and Hospital. The study was carried out in Anganwadi centers spanning the various districts and talukas of Goa state. Materials and Methods: The decayed, missing, and filled teeth (dmft) index was recorded in 3–5-year-old children along with treatment needs as per the modified WHO pro forma. Statistical Analysis: Statistical software (STATA) for data science by StataCorp LLC (version 17), descriptive statistics, and Chi-square test. Results: A total of 386 children were examined, out of which 47% had ECC. The prevalence of ECC was highest in Canacona and the least in Tiswadi talukas. The severity and occurrence of ECC were found to the proportional to age. With regard to treatment needs, 8.55% needed restoration of at least one surface, 10.88% needed restoration of 2 or more surfaces, 5.44% required a crown, 11.4% needed pulpal treatment, and 6.74% needed extractions. Within the dmft component, the percentage of decayed teeth was 46.89%, followed by filled (0.52%) and missing (0.52%) teeth. Conclusion: The prevalence and severity of ECC in children attending Anganwadi centers in Goa were found to be large and proportional with increasing age

Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis

Summary: The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings indicate that CQ induces p53- and Rab8b-dependent Par-4 secretion from normal cells for Par-4-dependent inhibition of metastatic tumor growth. : Burikhanov et al. identify the anti-malarial drug chloroquine (CQ) as a robust secretagogue of tumor suppressor Par-4. CQ-inducible Par-4 secretion is dependent on p53 and Rab8b for vesicle transport. Induction of Par-4 secretion provides an attractive option for the re-purposing of existing drugs for apoptosis and inhibition of tumor metastasis. Keywords: chloroquine, Par-4, p53, apoptosis, Rab8b, secretagogues, metastasis-inhibitio