Date of Award
Chemistry and Biochemistry
Pure sciences, Biological sciences
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Hierarchical phosphorylation of four Ser/Thr residues orchestrates the ubiquitination and proteasomal degradation of the transcriptional co-activator, β-catenin . To the best of our knowledge, β-catenin is the only known protein with this tetraphosphorylation motif (TPM). However, the sophistication of this scheme prompted our hypothesis that there are other proteins regulated by this TPM.
Herein, we identified two novel TPM-containing proteins, TAZ and KLF7. Characterization of the TAZ and KLF7 TPMs revealed significant similarities and differences with respect to the biochemical role of the β-catenin TPM and demonstrated a functional consequence of their TPMs within the TAZ- and KLF7-mediated inhibition of adipogenesis.
We also provide the first direct evidence that TAZ is highly phosphorylated. Using mass spectrometry, we identified ten TAZ phosphorylation sites, of which three mapped to the TPM. Additionally, we present preliminary functional analyses of phosphorylation sites adjacent to the 14-3-3 binding site and WW domain of TAZ.
Sykes, Catherine, "Biochemical and functional characterization of a tetra-phosphorylation motif" (2009). Electronic Theses and Dissertations. 7969.