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Alternative splicing in oncogenic kinases: from physiological functions to cancer

Sabine Druillennec1, Coralie Dorard, Alain Eychène

  • 1Institut Curie, 91405 Orsay, France.

Journal of Nucleic Acids
|October 19, 2011
PubMed

Insights

Alternative splicing significantly impacts oncogenic protein kinase function in cancer. This review highlights how normal and aberrant splicing events contribute to tumor progression and kinase deregulation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • The human kinome comprises 518 protein kinases, with several functioning as oncoproteins in human cancers.
  • Like other eukaryotic genes, oncogenes encoding protein kinases undergo alternative splicing in both coding and noncoding regions.

Purpose of the Study:

  • To illustrate the significant impact of alternative splicing on the physiological functions of oncogenic protein kinases.
  • To discuss the role of regular and aberrant alternative splicing in cancer development and progression.

Main Methods:

  • Review of existing literature and studies, including mouse genetic models.
  • Analysis of specific examples of membrane-bound tyrosine kinases and cytosolic protein kinases.
  • Examination of alternative splicing events implicated in oncogenic processes and kinase deregulation.

Main Results:

  • Alternative splicing affects the physiological functions of oncogenic protein kinases, as shown in mouse models.
  • Regular alternative splicing events can be implicated in oncogenic processes during tumor progression.
  • Aberrant splicing events are responsible for the deregulation of oncogenic kinase activity in cancers.

Conclusions:

  • Alternative splicing is a critical mechanism influencing the function of oncogenic protein kinases.
  • Both normal and aberrant splicing play roles in cancer development, progression, and kinase activity deregulation.

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