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The role of a newly identified SET domain-containing protein, SETD3, in oncogenesis

Zhangguo Chen1, Catherine T Yan, Yali Dou

  • 1Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO, USA.

Haematologica
|October 16, 2012
PubMed

Insights

SETD3, a protein with SET domains, can act as an oncogene when truncated, contributing to lymphoma development. Full-length SETD3, however, does not show oncogenic potential, highlighting the importance of its SET domain in carcinogenesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • SET domain proteins, including histone methyltransferases, are crucial in cellular processes.
  • Dysregulation of SET domain proteins like MLL1 is linked to cancer, while others like SETD2 may act as tumor suppressors.

Purpose of the Study:

  • To investigate the role of the SETD3 gene and its protein product in peripheral B-cell lymphomas.
  • To determine the oncogenic potential of full-length versus truncated SETD3 proteins.

Main Methods:

  • Analysis of gene translocations involving SETD3 in lymphoma samples.
  • Quantification of SETD3 mRNA expression in lymphoma.
  • Assessment of the oncogenic potential of SETD3 protein variants.
  • In vitro assays to determine SETD3's histone methyltransferase activity.

Main Results:

  • SETD3 was found to be involved in a translocation in p53-deficient peripheral B-cell lymphomas.
  • A truncated SETD3 mRNA lacking the SET domain was highly expressed in lymphoma.
  • The SET-less SETD3 protein exhibited oncogenic potential, unlike the full-length protein.
  • SETD3 demonstrated SET-domain dependent histone methyltransferase activity on histone 3.

Conclusions:

  • The SETD3 gene, particularly its truncated form, may play a significant role in carcinogenesis.
  • The SET domain is critical for SETD3's function and its potential involvement in cancer development.

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