Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

Musings from the Tribbles Research and Innovation Network

“…However, it seems implausible from structural data that this N-terminally truncated protein could adequately control ubiquitination of its target protein substrates (Figure 4B). As Peter Mace so eloquently explained at the second international symposium on Tribbles and Diseases [51], the αC-helix (amino acids 127−140) and β4 Conventional cDNA cloning and sequencing methodologies and RNA-seq data (Figure 4A) now clearly show that the TRIB1-203 transcript reflects splicing at a cryptic donor splice-site deep within intron 1 (Figures 2 and 4A). A re-appraisal of the proteincoding status and, thus, potential significance of this alternatively-spliced transcript is thus urgently needed to understand whether its expression might contribute, for example, to a cell's response to a diverse range of stimuli, including mitogens and pro-inflammatory cytokines [25,26].…”

“…However, it seems implausible from structural data that this N-terminally truncated protein could adequately control ubiquitination of its target protein substrates (Figure 4B). As Peter Mace so eloquently explained at the second international symposium on Tribbles and Diseases [51], the αC-helix (amino acids 127-140) and β4 strand (amino acids 146-151) of TRIB1 (Figure 4B) protect it from COP1-mediated ubiquitination and ensuing proteasome-mediated degradation. In brief, these two structural elements sequester the C-terminal COP1-binding motif, preventing it from recruiting COP1.…”

Trouble With Tribbles-1

“…There is a large body of work published on the functions of TRIB2 and TRIB3 that we will not discuss given our focus, but needless to say, the Tribbles research community is a burgeoning field, as evidenced by two recent international conferences that brought the global Tribbles community together. 12,13 Tribbles proteins were first described in Drosophila when multiple genetic screens revealed that trbl regulates the proteins string and slbo, the latter being the Drosophila homolog of the C/EBPα basic region-leucine zipper transcription factor in humans. [14][15][16] Subsequent work established that TRIB1 and TRIB2 can regulate the proteasomal degradation of C/EBPα and β by binding the E3 ubiquitin ligase COP1, which in turn ubiquitinates the target C/EBP proteins and promotes their proteasomal degradation.…”