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Tribbles in disease: Signaling pathways important for cellular function and neoplastic transformation

Takashi Yokoyama1, Takuro Nakamura

  • 1Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

Cancer Science
|February 23, 2011
PubMed

Insights

Tribbles proteins are conserved adaptors in cellular signaling, linking pathways like MAPK to C/EBP degradation. Research on these pseudokinases offers insights into treating leukemia and other disorders.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Genetics

Background:

  • Tribbles family genes encode highly conserved pseudokinases.
  • These proteins function as adaptors in crucial cellular signaling pathways, not direct kinases.
  • Tribbles proteins are implicated in both neoplastic and non-neoplastic human diseases.

Purpose of the Study:

  • To summarize the known functions of tribbles proteins in cellular processes.
  • To highlight the role of tribbles in human diseases, including leukemia, metabolic, and neurological disorders.
  • To underscore the potential of tribbles research for therapeutic development.

Main Methods:

  • Literature review and synthesis of existing research on tribbles family genes.
  • Analysis of tribbles' interactions within signaling pathways, such as the RAS/MAPK pathway.
  • Examination of tribbles' involvement in cellular processes and disease pathogenesis.

Main Results:

  • Tribbles act as adaptors, influencing pathways like MAPKK, C/EBP, ATF4, and CHOP.
  • Trib1 and Trib2 are identified as myeloid oncogenes potentially involved in human leukemia.
  • Tribbles proteins are linked to metabolic and neurological diseases, suggesting broader roles in homeostasis.

Conclusions:

  • Tribbles proteins serve as critical linkers in signaling pathways, e.g., Trib1 connects MAPK signaling to C/EBP degradation.
  • Further investigation into tribbles' molecular functions is essential.
  • Understanding tribbles' roles in cellular processes and diseases can inform novel therapeutic strategies for cancer and non-neoplastic conditions.

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