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Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
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Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

Published on: December 5, 2019

RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties

Elizabeth J Horn1, Amador Albor, Yuangang Liu

  • 1Department of Dermatology, Oregon Health and Science University, Portland, OR 97239, USA.

Carcinogenesis
|October 28, 2003
PubMed

Insights

Tripartite motif protein 32 (Trim32) is elevated in skin cancers and promotes cell survival by inhibiting ultraviolet B-induced apoptosis. This E3-ubiquitin ligase activity suggests a role in epidermal carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Tripartite motif protein 32 (Trim32) mRNA and protein expression is elevated in mouse models of epidermal carcinogenesis and human squamous cell carcinomas (SCCs).
  • Elevated Trim32 expression is frequently observed in experimental epidermal carcinogenesis, indicating its relevance to human cancer.
  • Trim32's role in skin cancer development and its potential as an E3-ubiquitin ligase are under investigation.

Purpose of the Study:

  • To investigate the role of Trim32 in epidermal carcinogenesis and its functional mechanisms.
  • To determine if Trim32 expression influences keratinocyte transformation, proliferation, and apoptosis.
  • To explore Trim32's E3-ubiquitin ligase activity in the context of ultraviolet B (UVB) radiation and tumor necrosis factor alpha (TNFα) signaling.

Main Methods:

  • Analysis of Trim32 mRNA and protein expression in mouse epidermal carcinogenesis models and human SCCs.
  • In vitro epidermal transformation assays and in vivo skin-grafting experiments with Trim32 transduction.
  • Assessment of apoptosis in keratinocytes and skin grafts following UVB exposure, with and without Trim32.
  • Investigation of Trim32's E3-ubiquitin ligase activity, including ubiquitylation and interaction with ubiquitylated proteins.

Main Results:

  • Transduced Trim32 increased colony formation in vitro and epidermal thickening in vivo, independent of proliferation.
  • Trim32 inhibited UVB-induced apoptosis of keratinocytes in vitro and in vivo, particularly the synergistic effect of TNFα.
  • Trim32 exhibited E3-ubiquitin ligase characteristics, including self-ubiquitylation and interaction with ubiquitylated proteins, enhanced by TNFα/UVB treatment.
  • Trim32's effects were not sufficient for tumorigenesis, even with p53 defects or phorbol ester treatment.

Conclusions:

  • Trim32 acts as an E3-ubiquitin ligase that promotes initiated cell survival in carcinogenesis by inhibiting UVB-induced TNFα apoptotic signaling.
  • Elevated Trim32 expression is a frequent event in epidermal carcinogenesis and is relevant to human skin cancer.
  • Trim32's anti-apoptotic function suggests a critical role in promoting the survival of damaged keratinocytes during UVB exposure, contributing to skin cancer development.

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