In previous studies we have reported that a high levelof expression of mot-2 protein results in malignant transformation of NIH 3T3 cells as analyzed by anchorage indeopendent growth and nude mice assays [Kaul et al....In previous studies we have reported that a high levelof expression of mot-2 protein results in malignant transformation of NIH 3T3 cells as analyzed by anchorage indeopendent growth and nude mice assays [Kaul et al., Oncogene, 17, 907-11, 1998]. Mot-2 was found to interact withtumor suppressor protein p53. The transient overexpression of mot-2 was inhibitory to transcriptional activationfunction of p53 [Wadhwa et al., J. Biol. Chem., 273, 2958691, 1998]. We demonstrate here that mot-2 transfectedstable clonse of NIH 3T3 that showed malignant propertiesindeed show inactivation of p53 function as assayed byexogenous p53 dependent reporter. The expression levelof p53 in response to UV-irradiation was lower in NIH3T3/mot-2 as compared to NIH 3T3 cells and also exhibited delay in reaching peak. furthermore, upon serumstarvation p53 was seen to translocate to the 11ucleus inNIH 3T3, but not in its mot-2 derivative. The data suggests that mot-2 mediated cytoplasmic sequestration andinactivation of p53 may operate, at least in part, for malignant phenotype of NIH 3T3/mot-2 cells.NIH 3T3/mot-2 cells show inactivation of p53 protein展开更多
Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections ...Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and ano-genital epithelia by high-risk展开更多
The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73,the two other members of the p53 family.Loss of functional p53 leads to the proliferation and...The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73,the two other members of the p53 family.Loss of functional p53 leads to the proliferation and survival of mature cells and progenitor or stem cells that accumulate genetic alterations,thus favoring tumorigenesis.p53 loss of function,observed in a wide variety of human tumor types,is frequently caused by missense mutations more frequently found in the DNA binding domain,but can also be due to the expression of a plethora of viral and cellular negative regulators.Human hepatocellular carcinoma(HCC)represents a specific situation,first because the TP53 gene mutations pattern exhibits a“hot spot”rarely found in other tumor types that is linked to Aflatoxin B1 exposure and,second,because many HCCs do not exhibit any TP53 mutation.Here,we provide an overview of the current knowledge about the inhibition of p53 functions by the N-terminal(ΔN)truncated forms of the family,and their role in the emergence and maintenance of pre-malignant cells with stem cell characteristics and in HCC development.We focus in particular on the Nanog-IGF1R-ΔNp73 axis that is associated with stem-like features in HCC cells and that may provide an attractive new therapeutic target and help to develop new biomarkers for HCC risk stratification,as well as preventive strategies.展开更多
文摘In previous studies we have reported that a high levelof expression of mot-2 protein results in malignant transformation of NIH 3T3 cells as analyzed by anchorage indeopendent growth and nude mice assays [Kaul et al., Oncogene, 17, 907-11, 1998]. Mot-2 was found to interact withtumor suppressor protein p53. The transient overexpression of mot-2 was inhibitory to transcriptional activationfunction of p53 [Wadhwa et al., J. Biol. Chem., 273, 2958691, 1998]. We demonstrate here that mot-2 transfectedstable clonse of NIH 3T3 that showed malignant propertiesindeed show inactivation of p53 function as assayed byexogenous p53 dependent reporter. The expression levelof p53 in response to UV-irradiation was lower in NIH3T3/mot-2 as compared to NIH 3T3 cells and also exhibited delay in reaching peak. furthermore, upon serumstarvation p53 was seen to translocate to the 11ucleus inNIH 3T3, but not in its mot-2 derivative. The data suggests that mot-2 mediated cytoplasmic sequestration andinactivation of p53 may operate, at least in part, for malignant phenotype of NIH 3T3/mot-2 cells.NIH 3T3/mot-2 cells show inactivation of p53 protein
基金supported by the Intramural Research Program of the National Institutes of HealthNational Cancer Institutethe Center for Cancer Research
文摘Dear Editor,Human papillomaviruses(HPV)are a large group(>200genotypes)of small double-stranded DNA viruses(https://pave.niaid.nih.gov/).Although infections by most HPV types are asymptomatic,persistent infections in cervical and ano-genital epithelia by high-risk
基金This work was supported by grants from 《Agence Nationale pour la Recherche sur le SIDA et les hepatites virales》(ANRS)(ECTZ117561)to Levrero M,from the Agence Nationale de la Recherche(ANR@TRACTION)to Levrero Mfrom the EU project(667273 HEP-CAR)to Levrero Mfrom the Ligue Nationale Contre le Cancer,Coordination Auvergne-Rhône-Alpes&Saône-et-Loire to Caron de Fromentel C and Levrero M.
文摘The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73,the two other members of the p53 family.Loss of functional p53 leads to the proliferation and survival of mature cells and progenitor or stem cells that accumulate genetic alterations,thus favoring tumorigenesis.p53 loss of function,observed in a wide variety of human tumor types,is frequently caused by missense mutations more frequently found in the DNA binding domain,but can also be due to the expression of a plethora of viral and cellular negative regulators.Human hepatocellular carcinoma(HCC)represents a specific situation,first because the TP53 gene mutations pattern exhibits a“hot spot”rarely found in other tumor types that is linked to Aflatoxin B1 exposure and,second,because many HCCs do not exhibit any TP53 mutation.Here,we provide an overview of the current knowledge about the inhibition of p53 functions by the N-terminal(ΔN)truncated forms of the family,and their role in the emergence and maintenance of pre-malignant cells with stem cell characteristics and in HCC development.We focus in particular on the Nanog-IGF1R-ΔNp73 axis that is associated with stem-like features in HCC cells and that may provide an attractive new therapeutic target and help to develop new biomarkers for HCC risk stratification,as well as preventive strategies.
