Dataset Information

Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators.

ABSTRACT: Cadherins are cell-cell adhesion proteins essential for the maintenance of tissue architecture and integrity, and their impairment is often associated with human cancer. Knowledge regarding regulatory mechanisms associated with cadherin misexpression in cancer is scarce. Specific features of the intronic-structure and intronic-based regulatory mechanisms in the cadherin superfamily are unidentified. This study aims at systematically characterizing the intronic portion of cadherin superfamily members and the identification of intronic regions constituting putative targets/triggers of regulation, using a bioinformatic approach and biological data mining. Our study demonstrates that the cadherin superfamily genes harbour specific characteristics in comparison to all non-cadherin genes, both from the genomic and transcriptional standpoints. Cadherin superfamily genes display higher average total intron number and significantly longer introns than other genes and across the entire vertebrate lineage. Moreover, in the human genome, we observed an uncommon high frequency of MIR (mammalian-wide interspersed repeats) and MaLR (mammalian-wide interspersed repeats, a subtype of LTR) regulatory-associated repetitive elements at 5'-located introns, concomitantly with increased de novo intronic transcription. Using this approach, we identified cadherin intronic-specific sites that may constitute novel targets/triggers of cadherin superfamily expression regulation. These findings pinpoint the need to identify mechanisms affecting particularly MIR and MaLR elements located in introns 2 and 3 of human cadherin genes, possibly important in the expression modulation of this superfamily in homeostasis and cancer.

SUBMITTER: Oliveira P

PROVIDER: S-EPMC3400724 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators.

Oliveira Patrícia P Sanges Remo R Huntsman David D Stupka Elia E Oliveira Carla C

European journal of human genetics : EJHG 20120208 8

Cadherins are cell-cell adhesion proteins essential for the maintenance of tissue architecture and integrity, and their impairment is often associated with human cancer. Knowledge regarding regulatory mechanisms associated with cadherin misexpression in cancer is scarce. Specific features of the intronic-structure and intronic-based regulatory mechanisms in the cadherin superfamily are unidentified. This study aims at systematically characterizing the intronic portion of cadherin superfamily mem ...[more]

PMID: 22317972

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Project description:BackgroundFunctional characterization of genes in important pathogenic bacteria such as Mycobacterium tuberculosis is imperative. Rv2135c, which was originally annotated as conserved hypothetical, has been found to be associated with membrane protein fractions of H37Rv strain. The gene appears to contain histidine phosphatase motif common to both cofactor-dependent phosphoglycerate mutases and acid phosphatases in the histidine phosphatase superfamily. The functions of many of the members of this superfamily are annotated based only on similarity to known proteins using automatic annotation systems, which can be erroneous. In addition, the motif at the N-terminal of Rv2135c is 'RHA' unlike 'RHG' found in most members of histidine phosphatase superfamily. These necessitate the need for its experimental characterization. The crystal structure of Rv0489, another member of the histidine phosphatase superfamily in M. tuberculosis, has been previously reported. However, its biochemical characteristics remain unknown. In this study, Rv2135c and Rv0489 from M. tuberculosis were cloned and expressed in Escherichia coli with 6 histidine residues tagged at the C terminal.ResultsCharacterization of the purified recombinant proteins revealed that Rv0489 possesses phosphoglycerate mutase activity while Rv2135c does not. However Rv2135c has an acid phosphatase activity with optimal pH of 5.8. Kinetic parameters of Rv2135c and Rv0489 are studied, confirming that Rv0489 is a cofactor dependent phosphoglycerate mutase of M. tuberculosis. Additional characterization showed that Rv2135c exists as a tetramer while Rv0489 as a dimer in solution.ConclusionMost of the proteins orthologous to Rv2135c in other bacteria are annotated as phosphoglycerate mutases or hypothetical proteins. It is possible that they are actually phosphatases. Experimental characterization of a sufficiently large number of bacterial histidine phosphatases will increase the accuracy of the automatic annotation systems towards a better understanding of this important group of enzymes.

Dataset Information

Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators.

Publications

Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators.

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