Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development

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Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development. / Martin-Blanco, N. M.; Checquolo, S.; Del Gaudio, F.; Palermo, R.; Franciosa, G.; Di Marcotullio, L.; Gulino, A.; Canelles, M.; Screpanti, I.

In: Cell Death and Disease, Vol. 5, e1472, 2014.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Martin-Blanco, NM, Checquolo, S, Del Gaudio, F, Palermo, R, Franciosa, G, Di Marcotullio, L, Gulino, A, Canelles, M & Screpanti, I 2014, 'Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development', Cell Death and Disease, vol. 5, e1472. https://doi.org/10.1038/cddis.2014.438

APA

Martin-Blanco, N. M., Checquolo, S., Del Gaudio, F., Palermo, R., Franciosa, G., Di Marcotullio, L., Gulino, A., Canelles, M., & Screpanti, I. (2014). Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development. Cell Death and Disease, 5, [e1472]. https://doi.org/10.1038/cddis.2014.438

Vancouver

Martin-Blanco NM, Checquolo S, Del Gaudio F, Palermo R, Franciosa G, Di Marcotullio L et al. Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development. Cell Death and Disease. 2014;5. e1472. https://doi.org/10.1038/cddis.2014.438

Author

Martin-Blanco, N. M. ; Checquolo, S. ; Del Gaudio, F. ; Palermo, R. ; Franciosa, G. ; Di Marcotullio, L. ; Gulino, A. ; Canelles, M. ; Screpanti, I. / Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development. In: Cell Death and Disease. 2014 ; Vol. 5.

Bibtex

@article{be23e85bdf03419e927d7f012bfffabc,
title = "Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development",
abstract = "Numb asymmetrically segregates at mitosis to control cell fate choices during development. Numb inheritance specifies progenitor over differentiated cell fates, and, paradoxically, also promotes neuronal differentiation, thus indicating that the role of Numb may change during development. Here we report that Numb nuclear localization is restricted to early thymocyte precursors, whereas timed appearance of pre-T-cell receptor (pre-TCR) and activation of protein kinase Cθ promote phosphorylationdependent Numb nuclear exclusion. Notably, nuclear localization of Numb in early thymocyte precursors favors p53 nuclear stabilization, whereas pre-TCR-dependent Numb nuclear exclusion promotes the p53 downmodulation essential for further differentiation. Accordingly, the persistence of Numb in the nucleus impairs the differentiation and promotes precursor cell death. This study reveals a novel regulatory mechanism for Numb function based on its nucleus-cytosol shuttling, coupling the different roles of Numb with different stages of T-cell development.",
author = "Martin-Blanco, {N. M.} and S. Checquolo and {Del Gaudio}, F. and R. Palermo and G. Franciosa and {Di Marcotullio}, L. and A. Gulino and M. Canelles and I. Screpanti",
year = "2014",
doi = "10.1038/cddis.2014.438",
language = "English",
volume = "5",
journal = "Cell Death & Disease",
issn = "2041-4889",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development

AU - Martin-Blanco, N. M.

AU - Checquolo, S.

AU - Del Gaudio, F.

AU - Palermo, R.

AU - Franciosa, G.

AU - Di Marcotullio, L.

AU - Gulino, A.

AU - Canelles, M.

AU - Screpanti, I.

PY - 2014

Y1 - 2014

N2 - Numb asymmetrically segregates at mitosis to control cell fate choices during development. Numb inheritance specifies progenitor over differentiated cell fates, and, paradoxically, also promotes neuronal differentiation, thus indicating that the role of Numb may change during development. Here we report that Numb nuclear localization is restricted to early thymocyte precursors, whereas timed appearance of pre-T-cell receptor (pre-TCR) and activation of protein kinase Cθ promote phosphorylationdependent Numb nuclear exclusion. Notably, nuclear localization of Numb in early thymocyte precursors favors p53 nuclear stabilization, whereas pre-TCR-dependent Numb nuclear exclusion promotes the p53 downmodulation essential for further differentiation. Accordingly, the persistence of Numb in the nucleus impairs the differentiation and promotes precursor cell death. This study reveals a novel regulatory mechanism for Numb function based on its nucleus-cytosol shuttling, coupling the different roles of Numb with different stages of T-cell development.

AB - Numb asymmetrically segregates at mitosis to control cell fate choices during development. Numb inheritance specifies progenitor over differentiated cell fates, and, paradoxically, also promotes neuronal differentiation, thus indicating that the role of Numb may change during development. Here we report that Numb nuclear localization is restricted to early thymocyte precursors, whereas timed appearance of pre-T-cell receptor (pre-TCR) and activation of protein kinase Cθ promote phosphorylationdependent Numb nuclear exclusion. Notably, nuclear localization of Numb in early thymocyte precursors favors p53 nuclear stabilization, whereas pre-TCR-dependent Numb nuclear exclusion promotes the p53 downmodulation essential for further differentiation. Accordingly, the persistence of Numb in the nucleus impairs the differentiation and promotes precursor cell death. This study reveals a novel regulatory mechanism for Numb function based on its nucleus-cytosol shuttling, coupling the different roles of Numb with different stages of T-cell development.

U2 - 10.1038/cddis.2014.438

DO - 10.1038/cddis.2014.438

M3 - Journal article

C2 - 25321479

AN - SCOPUS:84925810051

VL - 5

JO - Cell Death & Disease

JF - Cell Death & Disease

SN - 2041-4889

M1 - e1472

ER -

ID: 209090405