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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
Summary
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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