RESUMO
Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here, we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 may be attributed to its negative regulation of uL18, leading to p53 inactivation.
Assuntos
Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas Associadas aos Microtúbulos/genética , Fosfoproteínas/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Ribossômicas/genética , Proteína Supressora de Tumor p53/genética , Animais , Carcinogênese/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Cultivadas , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HEK293 , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/genética , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
As an adjunct to infection control in dental impression procedures, several manufacturers have incorporated disinfectants into irreversible hydrocolloid impression materials. However, these compounds have been shown to be tissue irritants and capable of producing allergic reactions. An anonymous, self-administered questionnaire was distributed to 56 second-year dental students who had used an irreversible hydrocolloid containing a quaternary ammonium compound as an antimicrobial (Jeltrate Plus) to make impressions during a summer preclinical occlusion course. Within the limitations of this report, the incorporation of a quaternary ammonium compound into an irreversible hydrocolloid impression material resulted in a greater incidence of dermal and mucosal irritation.