CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOACaptura de pantalla 2022 09 14 a las 10.27.10    

Molecular and cellular basis of the physio(patho)logy associated with the expression of intracellular antigens

Resumen de Investigación:

The regulation of the heterogeneity of the transcriptome and proteome is key stage on the way to understand differences in the diversity of proteins observed in organisms of similar genetic complexity. The intracellular antigens TIA1 (T-cell intracellular antigen 1) and TIAR/TIAL1 (TIA1 related/like protein) have been involved in the regulation of gene expression on different aspects of the control of RNA metabolism, such as: i) transcription through its interaction with DNA and RNA polymerase II; ii) alternative splicing of pre-mRNA through the selection of atypical 5’ splicing sites; iii) localization, stability and/or translation of eukaryotic mRNAs through the interaction with 5' and 3’ untranslatable regions; and iv) modulation of biological programmes for cell survival (inflammation, proliferation, apoptosis, cell stress or infections by viruses). As a consequence, the initial hypothesis -of the work line initiated twelve years ago-  it is that these proteins may play a fundamental role in controlling gene expression by regulating/modulating the dynamics of human transcriptome and proteome, their expression and function, in order to prevent situations which put aberrant cell viability at risk in patho-physiological situations such as stress-associated responses, tumorigenesis or aging and their related diseases. So today, our objective is to characterize the early and late cellular processes and molecular mechanisms in which TIA proteins participate and how they are involved to regulate/modulate cellular homeostasis via preventing the development and/or progression of deleterious phenotypes. Understanding the regulatory dynamics associated with these intracellular antigens could serve as the basis for identifying future therapeutic targets.


The multifunctional TIA proteins regulate gene expression and many relevant physiopathological events.


Expression of TIA proteins (isoforms b) suppresses in vivo tumor growth. (A-C) Workflow and plots of progression of tumor size after inoculation of TIA1/TIAR-expressing cells and doxycycline (DOX) treatment. (D) Histological sections and immunohistochemical characterization of xenografts tumors. (E and F) Workflow and plot of progression of tumor size after inoculation of TIAR-expressing cells and doxycycline (DOX) treatment.

If you are interested in joining our group, please write to: jmizquierdo@cbm.csic.es


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Alcalde GarcíaJosé1064534jalcalde(at)cbm.csic.esE.Ayudantes De Invest. De Los Oo.Publicos De Investigacion
Izquierdo JuárezJosé María1074512jmizquierdo(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación
Naranjo SanchezMª del Rocio1074530rnaranjo(at)cbm.csic.esM2
Ramos VelascoBeatriz1074512bramos(at)cbm.csic.esGJ-TL_Tec. Sup. Actividades Técn. y Prof.GP3

Relevant publications:

  • Carrascoso, I., Sánchez-Jiménez, C., Silion, E., Alcalde, J., and Izquierdo, J. M. (2019) A heterologous cell model for studying the role of T-cell intracellular antigen 1 in Welander distal myopathy. Mol. Cell. Biol. 39: e00299-18. doi: 10.1128/MCB.00299-18.
  • Carrascoso, I., Alcalde, J., Sánchez-Jiménez, C., González-Sánchez, P., and Izquierdo, J. M. (2017) T-cell intracellular antigens and Hu antigen R antagonistically modulate mitochondrial activity and dynamics by regulating optic atrophy 1 gene expression. Mol. Cell. Biol. 37: e00174-17. doi: 10.1128/MCB.00174-17.
  • Sánchez-Jiménez C., and Izquierdo, J. M. (2015) T-cell intracellular antigens in health and disease. Cell Cycle. 14: 2033-2043. doi: 10.1080/15384101.2015.1053668.
  • Sánchez-Jiménez, C., Ludeña, M. D., and Izquierdo, J. M. (2015) T-cell intracellular antigens function as tumor suppressor genes. Cell Death Dis. 6: e1669. doi: 10.1038/cddis.2015.43.
  • Carrascoso, I., Sánchez-Jiménez, C., and Izquierdo, J. M. (2014) Genome-wide profiling reveals a role for T-cell intracellular antigens TIA1 and TIAR in the control of translational specificity in HeLa cells. Biochem. J. 461: 43-50. doi: 10.1042/BJ20140227.
  • Carrascoso, I., Sánchez-Jiménez, C., and Izquierdo, J. M. (2014) Long-term reduction of T-cell intracellular antigens leads to increased beta-actin expression. Mol. Cancer. 13: R87. doi: 10.1186/1476-4598-13-90.
  • Izquierdo, J. M.* (*Corresponding author), Alcalde, J., Carrascoso, I., Reyes, R., and Ludeña, M. D. (2011) Knockdown of T-cell intracellular antigens triggers cell proliferation, invasion and tumour growth. Biochem. J. 435: 337-344. doi: 10.1042/BJ20101030.
  • Izquierdo, J. M. (2010) Heterogeneous ribonucleoprotein C displays a repressor activity mediated by T-cell intracellular antigen-1-related/like protein to modulate Fas exon 6 splicing through a mechanism involving Hu antigen R. Nucleic Acids Res. 38: 8001-8014. doi: 10.1093/nar/gkq698.
  • Reyes, R., Alcalde, J., and Izquierdo, J. M. (2009) Depletion of T-cell intracellular antigen proteins promotes cell proliferation. Genome Biol. 10: R87. doi: 10.1186/gb-2009-10-8- 90. doi: 10.1186/1476-4598-13-90.
  • Izquierdo, J. M. (2008) Fas splicing regulation during early apoptosis is linked to caspase-mediated cleavage of U2AF65. Mol. Biol. Cell. 19: 3299-3307. doi: 10.1091/mbc.E07-11-1125.

Doctoral theses:

  • Carmen Sánchez-Jiménez (2014). Caracterización de modelos celulares con pérdida y ganancia de función de las proteínas TIA1 y TIAR. Universidad Autónoma de Madrid. Director: José María Izquierdo Juárez.

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