Biomedical subjects

Raul Villanueva

Publications and source records attributed to Raul Villanueva.

3 recordsLinked to original sources

PubMed2006

Histone deacetylase 3 represses HTLV-1 tax transcription.

We examined the epigenetic mechanisms involved in human T-cell lymphotropic virus type 1 (HTLV-1) Tax expression. Blockade of histone deacetylation with trichostatin A (TSA) resulted in Tax upregulation. Using a chromatin immunoprecipitation (ChIP) assay, we verified local histone hyperacetylation at the HTLV-1 LTR in response to TSA. In agreement, HDAC3 transfection led to reductions in both Tax expression and histone acetylation. HDAC3 mutations and deletions spanning the catalytic site had variable ability to repress Tax, but HDAC activity was not essential for repression. Immunoprecipitation studies revealed that Tax co-exists in a complex containing both histone deacetylase 1 (HDAC1) and 3 (HDAC3). Our results suggest that HDACs may actively participate in the repression of HTLV-1 Tax transcription.

Acetylation↗

PubMed2005

Functional characterization of JMJD2A, a histone deacetylase- and retinoblastoma-binding protein.

To effectively direct targeted repression, the class I histone deacetylases (HDACs) associate with many important regulatory proteins. In this paper we describe the molecular characterization of a member of the Jumonji domain 2 (JMJD2) family of proteins, and demonstrate its binding to both class I HDACs and the retinoblastoma protein (pRb). JMJD2 proteins are characterized by the presence of two leukemia-associated protein/plant homeodomain (LAP/PHD) zinc fingers, one JmjN, one JmjC (containing an internal retinoblastoma-binding protein 2 (RBBP2)-like sequence), and two Tudor domains. The first member of this group, JMJD2A, is widely expressed in human tissues and cell lines, and high endogenous expression of JMJD2A mRNA was found in several cell types, including human T-cell lymphotropic virus 1 (HTLV-1)-infected cell lines. JMJD2A and JMJD2B exhibit cell type-specific responses to the HDAC inhibitor trichostatin A. We show that the JMJD2A protein associates in vivo with pRb and class I HDACs, and mediates repression of E2F-regulated promoters. In HTLV-1 virus-infected cells, we find that JMJD2A binds to the viral Tax protein. Antibodies to JMJD2A recognize the native protein but also a half-sized protein fragment, the latter up-regulated in THP-1 cells during the G(2)/M phase of the cell cycle. The ability of JMJD2A to associate with pRb and HDACs and potentiate pRb-mediated repression of E2F-regulated promoters implies an important role for this protein in cell proliferation and oncogenesis.

Amino Acid Sequence↗

PubMed2004

Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells.

We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.

Adolescent↗