Wednesday, 13th December 2017
Cell Biology and Immunology
  Molecular and cellular basis of the physio(patho)logy associated with the expression of intracellular antigens

 


Grupo-400

 


 

 

José María Izquierdo Juárez

ACompoGrupo

AListado

 

 

 

 

Research Summary:

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Characterization by massive poly(A+) sequencing of the transcriptomes associated with TIA1 or TIAR-knocked down HeLa cells.

    

 

 

 
     
 

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Polysome profiling analysis show global changes at the transcript and translation levels under TIA reduction in HeLa cells.

 

 

 

 

 

 

 

 

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 nine 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.


 

Publications:

  • Sánchez-Jiménez C, Izquierdo JM (2015). T-cell intracellular antigens in health and disease. Cell Cycle 14: 2033-2043.
  • 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.
  • 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, 90.
  • Núñez, M., Sánchez-Jiménez, C., Alcalde, J. and Izquierdo, J. M. (2014) Long-term reduction of T-cell intracellular antigens reveals a transcriptome associated with extracellular matrix and cell adhesion components. PLoS One 9, e113141.
  • Sánchez-Jiménez, C., Ludeña, M. D. and Izquierdo, J. M. (2015) T-cell intracellular antigens function as tumor suppressor genes. Cell Death Dis. 6; doi:10.1038/cddis.2015.43.

 

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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