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Full-Text Articles in Life Sciences

Mutant C. Elegans P53 Together With Gain-Of-Function Glp-1/Notch Decreases Uvc-Damage-Induced Germline Cell Death But Increases Parp Inhibitor-Induced Germline Cell Death, Jorge Canar, Prima Manandhar-Sasaki, Jill Bargonetti Oct 2022

Mutant C. Elegans P53 Together With Gain-Of-Function Glp-1/Notch Decreases Uvc-Damage-Induced Germline Cell Death But Increases Parp Inhibitor-Induced Germline Cell Death, Jorge Canar, Prima Manandhar-Sasaki, Jill Bargonetti

Publications and Research

The TP53 gene is mutated in over 50% of human cancers, and the C. elegans p53-1 (cep-1) gene encodes the ortholog CEP-1. CEP-1 is activated by ultraviolet type C (UVC)-induced DNA damage and activates genes that induce germline apoptosis. UVC treatment of gain-of-function glp-1(ar202gf)/Notch tumorous animals reduces germline stem cell numbers (and overall tumor size), while UVC treatment of double-mutant cep-1/p53(gk138);glp-1/Notch(ar202gf) increases DNA damage adducts and stem cell tumor volume. We compared UVC-induced mitotic stem cell death and animal lifespans for the two different C. elegans tumorous strains. C. elegans stem cell compartment death has never been observed, and we …


Nuclear Tau, P53 And Pin1 Regulate Parn-Mediated Deadenylation And Gene Expression, Jorge Baquero, Sophia Varriano, Martha Ordonez, Pawel Kuczaj, Michael R. Murphy, Gamage Aruggoda, Devon Lundine, Viktoriya Morozova, Ali Elhadi Makki, Alejandra Del C. Alonso, Frida E. Kleiman Oct 2019

Nuclear Tau, P53 And Pin1 Regulate Parn-Mediated Deadenylation And Gene Expression, Jorge Baquero, Sophia Varriano, Martha Ordonez, Pawel Kuczaj, Michael R. Murphy, Gamage Aruggoda, Devon Lundine, Viktoriya Morozova, Ali Elhadi Makki, Alejandra Del C. Alonso, Frida E. Kleiman

Publications and Research

While nuclear tau plays a role in DNA damage response (DDR) and chromosome relaxation, the mechanisms behind these functions are not fully understood. Here, we show that tau forms complex(es) with factors involved in nuclear mRNA processing such as tumor suppressor p53 and poly(A)-specific ribonuclease (PARN) deadenylase. Tau induces PARN activity in different cellular models during DDR, and this activation is further increased by p53 and inhibited by tau phosphorylation at residues implicated in neurological disorders. Tau’s binding factor Pin1, a mitotic regulator overexpressed in cancer and depleted in Alzheimer’s disease (AD), also plays a role in the activation of …


Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane Nov 2018

Il-24 Promotes Apoptosis Through Camp-Dependent Pka Pathways In Human Breast Cancer Cells, Leah Persaud, Jason Mighty, Xuelin Zhong, Ashleigh Francis, Marifer Mendez, Hilal Muharam, Stephen M. Redenti, Dibash Das, Bertal Huseyin Aktas, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of …


Translation Control By P53, Justina Kasteri, Dibash K. Das, Xuelin Zhong, Leah Persaud, Ashleigh Francis, Hilal Muharam, Moira Sauane May 2018

Translation Control By P53, Justina Kasteri, Dibash K. Das, Xuelin Zhong, Leah Persaud, Ashleigh Francis, Hilal Muharam, Moira Sauane

Publications and Research

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the …


Resveratrol And Pterostilbene Exhibit Anticancer Properties Involving The Downregulation Of Hpv Oncoprotein E6 In Cervical Cancer Cells, Kaushiki Chatterjee, Dina Alsharif, Christina Mazza, Palwasha Syar, Mohamed Al Sharif, Jimmie E. Fata Feb 2018

Resveratrol And Pterostilbene Exhibit Anticancer Properties Involving The Downregulation Of Hpv Oncoprotein E6 In Cervical Cancer Cells, Kaushiki Chatterjee, Dina Alsharif, Christina Mazza, Palwasha Syar, Mohamed Al Sharif, Jimmie E. Fata

Publications and Research

Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents …


Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti May 2017

Estrogen-Activated Mdm2 Disrupts Mammary Tissue Architecture Through A P53-Independent Pathway, Nandini Kundu, Angelika Brekman, Jun Yeob Kim, Gu Xiano, Chong Gao, Jill Bargonetti

Publications and Research

The Cancer Genome Atlas (TCGA) data indicate that high MDM2 expression correlates with all subtypes of breast cancer. Overexpression of MDM2 drives breast oncogenesis in the presence of wild-type or mutant p53 (mtp53). Importantly, estrogen-receptor positive (ER+) breast cancers overexpress MDM2 and estrogen mediates this expression. We previously demonstrated that this estrogen-MDM2 axis activates the proliferation of breast cancer cell lines T47D (mtp53 L194F) and MCF7 (wild-type p53) in a manner independent of increased degradation of wildtype p53 (ie, p53-independently). Herein we present data supporting the role of the estrogen-MDM2 axis in regulating cell proliferation and mammary tissue architecture of …


Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan Jul 2016

Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan

Publications and Research

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and …