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Nuclear Phosphoproteome Reveals Prolyl Isomerase PIN1 as a Modulator of Oncogene-Induced Senescence.
Mohallem, Rodrigo; Aryal, Uma K.
Afiliação
  • Mohallem R; Department of Comparative Pathobiology, Purdue University, West Lafayette, USA; Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, USA.
  • Aryal UK; Department of Comparative Pathobiology, Purdue University, West Lafayette, USA; Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, USA. Electronic address: uaryal@purdue.edu.
Mol Cell Proteomics ; 23(2): 100715, 2024 Feb.
Article em En | MEDLINE | ID: mdl-38216124
ABSTRACT
Mammalian cells possess intrinsic mechanisms to prevent tumorigenesis upon deleterious mutations, including oncogene-induced senescence (OIS). The molecular mechanisms underlying OIS are, however, complex and remain to be fully characterized. In this study, we analyzed the changes in the nuclear proteome and phosphoproteome of human lung fibroblast IMR90 cells during the progression of OIS induced by oncogenic RASG12V activation. We found that most of the differentially regulated phosphosites during OIS contained prolyl isomerase PIN1 target motifs, suggesting PIN1 is a key regulator of several promyelocytic leukemia nuclear body proteins, specifically regulating several proteins upon oncogenic Ras activation. We showed that PIN1 knockdown promotes cell proliferation, while diminishing the senescence phenotype and hallmarks of senescence, including p21, p16, and p53 with concomitant accumulation of the protein PML and the dysregulation of promyelocytic leukemia nuclear body formation. Collectively, our data demonstrate that PIN1 plays an important role as a tumor suppressor in response to oncogenic ERRasG12V activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptidilprolil Isomerase / Proteoma Limite: Animals / Humans Idioma: En Revista: Mol Cell Proteomics Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptidilprolil Isomerase / Proteoma Limite: Animals / Humans Idioma: En Revista: Mol Cell Proteomics Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos