Dr Sumana Sanyal and her team at HKU Pasteur Research Pole, in collaboration with colleagues from the Whitehead Institute for Biomedical Research/MIT in Cambridge have published a new study in the Proceedings of the National Academy of Sciences of the USA (PNAS, published online before print on January 25, 2016). What maintains the magnitude and duration of signaling in T lymphocytes? It is already known that a large number of post-translational modifications regulate the cell fate from engagement of the T-cell receptor (TCR) to transcription of genes associated with the immune response. Among others, phosphorylations, dephosphorylations, calcium signaling, translocation of transcription factors… and of course ubiquitylations and deubiquitylations play a significant role. The current research aimed at identifying deubiquitylating enzymes that participate in this pathway. Deubiquitylation is the removal of a small protein, ubiquitin, or a chain of ubiquitin molecules, conjugated to substrate proteins in order to affect their function: inhibit or enhance protein interactions, modify the proteins cellular location, signal for protein degradation, or adjust proteins activity. While screening for deubiquitylases involved in TCR signaling, the team identified two proteins which had previously never been described in this pathway, as well as two of their substrates: TCR adaptor proteins. They show that one of these deubiquitylation enzyme, the ubiquitin-specific peptidase 12 (Usp12), plays a critical role in maintaining the TCR complex at the cell surface. Hence, the study indicates that deubiquitylases are stakeholders to take on board when considering fine-tuning of signaling cascades.
Proposed model for Usp12 function in the pathway of TCR signaling (Jahan et al. 2016)
To find the publication:
Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling. Jahan AS, Lestra M, Swee LK, Fan Y, Lamers MM, Tafesse FG, Theile CS, Spooner E, Bruzzone R, Ploegh HL, Sanyal S. PNAS 2016 Jan. doi: 10.1073/pnas.1521763113