The role of NUPR1 in lymphocyte proliferation and apoptosis

Milica Vujičić, Bobana Vasić, Ivana Nikolić, Tamara Saksida, Ivana Stojanović

Abstract


Nuclear protein 1 (NUPR1) is a transcription cofactor that senses stressful conditions and modulates cellular response by promoting or inhibiting apoptosis. NUPR1 is usually highly expressed in tumor cells where it enables them to adapt and resist environmental stress or chemotherapeutic compounds. NUPR1 can be involved in cell proliferation. Data about the involvement of NUPR1 in the proliferation and apoptosis of lymphocytes are scarce. Therefore, in this study we focused on the role of NUPR1 in lymphocyte physiology and found that NUPR1 might be involved in the initiation of their proliferation. Lymphocytes were isolated from the cervical lymph nodes of C57BL/6 mice. NUPR1 expression subsided 24 h after the induction of proliferation by a mitogen. Also, stressful conditions after cell isolation led to increased NUPR1 mRNA and protein expression in vitro that coincided with cell apoptosis. Similarly, apoptosis induction by staurosporine, a broad-range protein kinase inhibitor, led to increased NUPR1 expression. In addition, NUPR1 inhibition by small-interfering RNA prevented the staurosporine-induced apoptosis (judging from decreased caspase activity) in the whole cell population of cervical lymph nodes. However, NUPR1 absence was irrelevant to the induction of apoptosis in CD3+ T lymphocytes, suggesting that NUPR1 is probably a mediator of apoptosis in other immune cell populations within the lymph node, such as B lymphocytes. In conclusion, our results suggest that NUPR1 is important for the initiation of lymphocyte cell division and for the apoptotic process of non-T cells during stressful conditions.

https://doi.org/10.2298/ABS160707096V

Received: July 7, 2016; Revised: October 7, 2016; Accepted: October 7, 2016; Published online: October 14, 2016

How to cite this article: Vujičić M, Vasić B, Nikolić I, Saksida T, Stojanović I. The role of NUPR1 in lymphocyte proliferation and apoptosis. Arch Biol Sci. 2017;69(2):261-7.


Keywords


apoptosis; cervical lymph node; apoptosis; lymphocyte; nuclear protein 1; proliferation

Full Text:

PDF

References


Hamidi T, Algul H, Cano CE, Sandi MJ, Molejon MI, Riemann M, Calvo EL, Lomberk G, Dagorn JC, Weih F, Urrutia R, Schmid RM, Iovanna JL. Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest. 2012;122(6):2092-103.

Malicet C, Giroux V, Vasseur S, Dagorn JC, Neira JL, Iovanna JL. Regulation of apoptosis by the p8/prothymosin alpha complex. Proc Natl Acad Sci U S A. 2006;103(8):2671-6.

Mohammad HP, Seachrist DD, Quirk CC, Nilson JH. Reexpression of p8 contributes to tumorigenic properties of pituitary cells and appears in a subset of prolactinomas in transgenic mice that hypersecrete luteinizing hormone. Mol Endocrinol. 2004;18(10):2583-93.

Su SB, Motoo Y, Iovanna JL, Xie MJ, Mouri H, Ohtsubo K, Matsubara F, Sawabu N. Expression of p8 in human pancreatic cancer. Clin Cancer Res. 2001;7(2):309-13.

Pommier RM, Gout J, Vincent DF, Cano CE, Kaniewski B, Martel S, Rodriguez J, Fourel G, Valcourt U, Marie JC, Iovanna JL, Bartholin L. The human NUPR1/P8 gene is transcriptionally activated by transforming growth factor beta via the SMAD signalling pathway. Biochem J. 2012;445(2):285-93.

Carracedo A, Lorente M, Egia A, Blazquez C, Garcia S, Giroux V, Malicet C, Villuendas R, Gironella M, González-Feria L, Piris MA, Iovanna JL, Guzmán M, Velasco G. The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell. 2006;9(4):301-12.

Salazar M, Carracedo A, Salanueva IJ, Hernandez-Tiedra S, Lorente M, Egia A, Vázquez P, Blázquez C, Torres S, García S, Nowak J, Fimia GM, Piacentini M, Cecconi F, Pandolfi PP, González-Feria L, Iovanna JL, Guzmán M, Boya P, Velasco G. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells. J Clin Invest. 2009;119(5):1359-72.

Barbosa-Sampaio HC, Liu B, Drynda R, Rodriguez de Ledesma AM, King AJ, Bowe JE, Malicet C, Iovanna JL, Jones PM, Persaud SJ, Muller DS. NUPR1 deletion protects against glucose intolerance by increasing beta cell mass. Diabetologia. 2013;56(11):2477-86.

Sambasivan R, Cheedipudi S, Pasupuleti N, Saleh A, Pavlath GK, Dhawan J. The small chromatin-binding protein p8 coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter. J Cell Sci. 2009;122(Pt 19):3481-91.

Sambasivan R, Pavlath GK, Dhawan J. A gene-trap strategy identifies quiescence-induced genes in synchronized myoblasts. J Biosci. 2008;33(1):27-44.

Weis S, Schlaich TC, Dehghani F, Carvalho T, Sommerer I, Fricke S, Kahlenberg F, Mössner J, Hoffmeister A. p8 deficiency causes siderosis in spleens and lymphocyte apoptosis in acute pancreatitis. Pancreas. 2014;43(8):1277-85.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.

Stojanovic I, Saksida T, Nikolic I, Nicoletti F, Stosic-Grujicic S. Macrophage migration inhibitory factor deficiency protects pancreatic islets from cytokine-induced apoptosis in vitro. Clin Exp Immunol. 2012;169(2):156-63.

Souvannavong V, Lemaire C, Chaby R. Lipopolysaccharide protects primary B lymphocytes from apoptosis by preventing mitochondrial dysfunction and Bax translocation to mitochondria. Infect Immun. 2004;72(6):3260-6.

Belmokhtar CA, Hillion J, Segal-Bendirdjian E. Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms. Oncogene. 2001;20(26):3354-62.

Nogueira CV, Lindsten T, Jamieson AM, Case CL, Shin S, Thompson CB, Roy CR.Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila. PLoS Pathog. 2009;5(6):e1000478.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 ARCHIVES OF BIOLOGICAL SCIENCES

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.