Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
AI Summary:
The study demonstrates a direct role of the ciliary protein UNC119 in trafficking LCK to the immunological synapse. Inhibiting UNC119 reduces localisation of LCK without impairing LCK phosphorylation and reduces T-cell receptor signal transduction.AI Topics:
T-cell receptor recognition of cognate peptide–MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction. Moreover, as LCK is a driver in T acute lymphocytic leukaemia, it is important to understand its regulation. Here, we demonstrate a direct role of the ciliary protein UNC119 in trafficking LCK to the immunological synapse. Inhibiting UNC119 reduces localisation of LCK without impairing LCK phosphorylation and reduces T-cell receptor signal transduction. Although important for initial LCK reorganisation, activated CD8+ T cells retained their ability to kill target tumour cells when UNC119 was inhibited. UNC119 was also needed to sustain proliferation in patient-derived T-ALL cells. UNC119 may therefore represent a novel therapeutic target in T acute lymphocytic leukaemia, which alters the subcellular localisation of LCK in T acute lymphocytic leukaemia cells but preserves the function of existing cytotoxic lymphocytes.
Samarakoon, Youhan
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listYelland, Tamas
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listGarcia-Gonzalez, Esther
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listJusto-Junior, Amauri da Silva
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listMahmood, Mahnoor
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listManoharan, Anand
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listPatterson, Shaun D.
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
See full publications listSerafin, Valentina
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listGammage, Payam A.
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listMarmiroli, Sandra
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listHalsey, Christina
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
Apps, John and Halsey, Christina and Pritchard Jones, Kathy and Atun, Rifat and Shanmugavadivel, Dhurgshaarna and Oliver, Kathy and Vedhara, Kavita and Liu, JoFen and Ball-Gamble, Ashley and Ranasinghe, Neil and Polanco, Angela and Adamski, Jenny and Green, Adam and Walker, David A. (2024) A review calling for research directed at early detection of childhood cancers: the clinical, scientific, and economic arguments for population screening and surveillance. EJC Paediatric Oncology, 4: 100191. ISSN 2772-610X
Anastasopoulou, Stavroula and Swann, Gemma and Andres-Jensen, Liv and Attarbaschi, Andishe and Barzilai-Birenboim, Shlomit and Erdelyi, Daniel J. and Escherich, Gabriele and Hamadeh, Lina and Harila, Arja and Lopez-Lopez, Elixabet and McGowan, Sheena and Möricke, Anja and Putti, Caterina and Sagi, Judit C. and Schmiegelow, Kjeld and Ullrich, Nicole J. and van der Sluis, Inge M. and ul-Ain Wahid, Qurat and Winick, Naomi and Sramkova, Lucie and Zalcberg, Yair and Zapotocka, Ester and Bhojwani, Deepa and Halsey, Christina (2024) Severe steroid-related neuropsychiatric symptoms during paediatric acute lymphoblastic leukaemia therapy—An observational Ponte di Legno Toxicity Working Group Study. British Journal of Haematology, 205 (4). pp. 1450-1459. ISSN 0007-1048
See full publications listIsmail, Shehab
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
See full publications listRoberts, Edward W.
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
Lukoszek, Radoslaw and Inesta-Vaquera, Francisco and Brett, Natasha J.M. and Liang, Shang and Hepburn, Lydia A. and Hughes, David J. and Pirillo, Chiara and Roberts, Edward W. and Cowling, Victoria H. (2024) CK2 phosphorylation of CMTR1 promotes RNA cap formation and influenza virus infection. Cell Reports, 43 (7): 114405. ISSN 2639-1856
See full publications listAvailable under License Creative Commons Attribution.
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