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Updated: Jul 5, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

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Nuclear Phosphoproteome Reveals Prolyl Isomerase PIN1 as a Modulator of Oncogene-Induced Senescence

Rodrigo Mohallem1, Uma K Aryal1

  • 1Department of Comparative Pathobiology, Purdue University, West Lafayette, USA; Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, USA.

Molecular & Cellular Proteomics : MCP
|January 12, 2024
PubMed

Insights

Prolyl isomerase PIN1 acts as a tumor suppressor by regulating oncogene-induced senescence (OIS). PIN1 knockdown impairs OIS hallmarks, promoting cell proliferation and tumor growth.

Area of Science:

  • Cellular senescence
  • Tumorigenesis
  • Molecular mechanisms of cancer

Background:

  • Mammalian cells have intrinsic tumor suppression mechanisms like oncogene-induced senescence (OIS).
  • The molecular pathways governing OIS are intricate and not fully understood.
  • Oncogenic RAS activation triggers OIS, a crucial anti-cancer response.

Purpose of the Study:

  • To investigate the nuclear proteome and phosphoproteome changes during OIS progression.
  • To identify key regulators of OIS, particularly those targeted by prolyl isomerase PIN1.
  • To elucidate the role of PIN1 in the context of oncogenic RAS-induced senescence.

Main Methods:

  • Analysis of nuclear proteome and phosphoproteome in IMR90 lung fibroblast cells.
  • Induction of OIS using oncogenic RAS (RASG12V) activation.
  • Assessment of PIN1's role through knockdown experiments and evaluation of senescence markers.

Main Results:

  • Most differentially regulated phosphosites during OIS contain PIN1 target motifs.
  • PIN1 knockdown promotes cell proliferation and reduces senescence markers (p21, p16, p53).
  • PIN1 inhibition leads to PML protein accumulation and dysregulated promyelocytic leukemia nuclear body formation.

Conclusions:

  • PIN1 is a critical regulator of OIS, targeting promyelocytic leukemia nuclear body proteins.
  • PIN1 functions as a tumor suppressor in response to oncogenic RAS activation.
  • Targeting PIN1 could offer new therapeutic strategies for RAS-driven cancers.
Keywords:
fibroblastnuclear phosphoproteomeoncogene-induced senescenceprolyl isomerasepromyelocytic leukemia nuclear body

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