Biomedical subjects

Baldo Oliva

Publications and source records attributed to Baldo Oliva.

6 recordsLinked to original sources

PubMed2025

Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control.

Entry into the cell cycle requires activation of G1 cyclin-dependent kinases (CDKs) and the G1/S transcriptional program. In fission yeast, the MBF complex is the main transcription factor driving early cell-cycle gene expression. MBF-dependent transcription is activated in metaphase and repressed at the end of S phase by a feedback loop involving the cyclin Cig2 and co-repressors Nrm1 and Yox1. While replicative stress inactivates Yox1 via phosphorylation, the mechanism that activates MBF during an unperturbed cell cycle remains unclear. Here, we identify Nrm1 as the key target of cell cycle regulation in a two-step control mechanism. First, CDK1 phosphorylates Nrm1 in metaphase, leading to its release-along with Yox1-from chromatin. Second, unphosphorylated Nrm1, generated either by dephosphorylation or de novo synthesis, is degraded during anaphase, preventing its re-association with MBF until the end of the next S phase. Together, these parallel pathways create a precisely timed window of MBF activation, ensuring proper cell cycle progression and preserving genomic stability.

Schizosaccharomyces↗

PubMed2006

Identification of function-associated loop motifs and application to protein function prediction.

MOTIVATION: The detection of function-related local 3D-motifs in protein structures can provide insights towards protein function in absence of sequence or fold similarity. Protein loops are known to play important roles in protein function and several loop classifications have been described, but the automated identification of putative functional 3D-motifs in such classifications has not yet been addressed. This identification can be used on sequence annotations. RESULTS: We evaluated three different scoring methods for their ability to identify known motifs from the PROSITE database in ArchDB. More than 500 new putative function-related motifs not reported in PROSITE were identified. Sequence patterns derived from these motifs were especially useful at predicting precise annotations. The number of reliable sequence annotations could be increased up to 100% with respect to standard BLAST. CONTACT: boliva@imim.es SUPPLEMENTARY INFORMATION: Supplementary Data are available at Bioinformatics online.

Amino Acid Sequence↗

PubMed2006

PIANA: protein interactions and network analysis.

UNLABELLED: We present a software framework and tool called Protein Interactions And Network Analysis (PIANA) that facilitates working with protein interaction networks by (1) integrating data from multiple sources, (2) providing a library that handles graph-related tasks and (3) automating the analysis of protein-protein interaction networks. PIANA can also be used as a stand-alone application to create protein interaction networks and perform tasks such as predicting protein interactions and helping to identify spots in a 2D electrophoresis gel. AVAILABILITY: PIANA is under the GNU GPL. Source code, database and detailed documentation may be freely downloaded from http://sbi.imim.es/piana.

Computer Graphics↗

PubMed2006

Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL.

Bcl-xL gene induces metastasis in the lung, lymph nodes and bone when breast cancer cells are inoculated in Nude Balb/c mice. In an attempt to identify the molecules required for diverse metastatic foci, we compared gene expression levels in tumor cells and metastatic variants with a cDNA GeneFilter containing 4000 known genes. The transcriptional regulators of alpha1-fetoprotein transcription factor, TBP-associated factor 172 (TAF-172) and the human zinc finger protein 5 (ZFP5) were downregulated. The expression of TAF-172 was inversely proportional to Bcl-xL expression (ANOVA P < 0.0001) and metastatic activity (ANOVA P < 0.0001). A protein interaction program allowed us to functionally associate Bcl-xL and TAF through TATA-binding protein (TBP), suggesting that Bcl-xL connects metabolic pathways with transcriptional machinery. The prediction included proteins involved in apoptosis, electron transfer, kinases and transcription factors. These results indicate that the selection of diverse metastatic cells from the broad spectrum of tumor cell leads to the underexpression of certain transcriptional regulators that might act as adaptor molecules to different microenvironments, and indicate that the synergistic activity of several genes is needed for the selection process in several metastatic foci.

Animals↗

PubMed2005

Prediction of protein-protein interactions using distant conservation of sequence patterns and structure relationships.

MOTIVATION: Given that association and dissociation of protein molecules is crucial in most biological processes several in silico methods have been recently developed to predict protein-protein interactions. Structural evidence has shown that usually interacting pairs of close homologs (interologs) physically interact in the same way. Moreover, conservation of an interaction depends on the conservation of the interface between interacting partners. In this article we make use of both, structural similarities among domains of known interacting proteins found in the Database of Interacting Proteins (DIP) and conservation of pairs of sequence patches involved in protein-protein interfaces to predict putative protein interaction pairs. RESULTS: We have obtained a large amount of putative protein-protein interaction (approximately 130,000). The list is independent from other techniques both experimental and theoretical. We separated the list of predictions into three sets according to their relationship with known interacting proteins found in DIP. For each set, only a small fraction of the predicted protein pairs could be independently validated by cross checking with the Human Protein Reference Database (HPRD). The fraction of validated protein pairs was always larger than that expected by using random protein pairs. Furthermore, a correlation map of interacting protein pairs was calculated with respect to molecular function, as defined in the Gene Ontology database. It shows good consistency of the predicted interactions with data in the HPRD database. The intersection between the lists of interactions of other methods and ours produces a network of potentially high-confidence interactions.

Algorithms↗

PubMed2005

Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis.

Bcl-x(L) protein plays a role in breast cancer dormancy, promoting survival of cells in metastatic foci by counteracting the proapoptotic signals in the microenvironment. The aim of this study was to identify phenotypes mediated by Bcl-x(L) in breast cancer cells that enhance in vivo survival of clinical metastases. 435/Bcl-x(L) or 435/Neo human breast cancer cells were injected into the inguinal mammary gland of nude mice, and tumors, metastases in lymph node, lung, and bone, and bloodstream surviving cells were examined. Proteomic analysis identified 17 proteins that were overexpressed (more than twofold) or underexpressed (less than twofold) in metastases. A protein interaction program allowed us to functionally associate peroxiredoxin 3, peroxiredoxin 2, carbonyl reductase 3, and enolase 1, suggesting a role for cellular responses to oxidative stress in metastasis organ selection. The prediction included proteins involved in redox systems, kinase pathways, and the ATP synthase complex. Furthermore, the interaction of redox proteins with enolase 1 suggests a connection between glycolysis and antioxidant pathways, enabling achievement of a high metastatic activity. In conclusion, Bcl-x(L) mediates a phenotype in which redox pathways and glycolysis are coupled to protect breast cancer metastatic cells during transit from the primary tumor to the metastatic state.

Animals↗