Sequence, gene structure, and expression pattern of CTNNBL1, a minor-class intron-containing gene - evidence for a role in apoptosis
ABSTRACT We have identified and characterized a cDNA designated CTNNBL1 (catenin (cadherin-associated protein), beta-like 1) coding for a protein of 563 amino acids having predicted structural homology to beta-catenin and other armadillo (arm) family proteins. CTNNBL1 is expressed in multiple human tissues, and its sequence is conserved across widely divergent species. The human CTNNBL1 gene on chromosome 20q11.2 contains 16 exons spanning > 178 kb. Intron 4 is a minor-class intron bearing AT at the 5' splice site and AC at the 3' splice site. An acidic domain, as well as a putative bipartite nuclear localization signal, a nuclear export signal, a leucine-isoleucine zipper, and phosphorylation motifs are present in the protein sequence. Transient expression of CTNNBL1 in CHO cells results in localization to the nucleus and apoptosis. The rate of cell death was higher when cells were transfected with a carboxy-terminal fragment of CTNNBL1, suggesting that the apoptosis-inducing activity is a function of this region.
SourceAvailable from: Gianni Barcaccia[Show abstract] [Hide abstract]
ABSTRACT: In contrast to sexual reproduction, apomixis bypasses meiosis and egg cell fertilization. Gametophytic apomixis occurs with the parthenogenetic deve-lopment of unreduced egg cells from apomeiotic embryo sacs originating from a nucellar somatic cell (apospory) or a megaspore mother cell with no, or modified, meiosis (diplospory). Apomeiosis, along with parthenogene-sis, excludes segregation and recombination during meiosis and fertiliza-tion. Thus, understanding the genetic control and the molecular mecha-nisms underlying apomeiosis is critical for the comprehension of apomixis as a whole. In this paper we review the available data on apospory in the facultative apomictic species Kentucky bluegrass (Poa pratensis L.) and on diplospory in reproductive mutants of the sexual species alfalfa (Medicago sativa L.). Our recent acquisitions on candidate genes for apomeiosis are reported and strategies for elucidating the inheritance of this trait by means of genomics and expression studies are presented and discussed. In parti-cular, experimental data focus on PpSERK and MsMob1 genes. We docu-ment that PpSERK transcripts are specifically expressed in the megaspore mother cells of sexual genotypes and in the aposporic initials of sexual genotypes, suggesting that PpSERK plays a role in early stages of embryo sac development. Moreover, the altered expression of MsMob1 in ovules of a reproductive mutant producing diplosporic eggs is reported, and the implication of MsMob1 proteins in programmed cell death of meiotic megaspores is also considered.Apomixis: Evolution, Mechanisms and Perspectives., Volume 147. edited by Hörandle E., Grossniklaus U., Van Dijk P., Sharbel T.F., 01/2007: chapter Chapter V.: pages pp. 93-116; Intl. Association of Plant Taxonomy – Koeltz Scientific Books, Vienna (Austria)., ISBN: 978-3-906166-60-5
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ABSTRACT: Ovarian stimulation with FSH combined with an appropriate period of FSH withdrawal (coasting) before ovum pick-up (OPU) now appears to be a successful way to obtain oocytes with high developmental competence in bovine. Recent results showed that extending follicular growth by only 24 hours has a detrimental effect on oocyte quality as shown by the reduced blastocyst formation rate. Even though these treatments are initiated during the luteal phase with low LH level, the small LH pulsatility present at that time could potentially impact follicular development as well as oocyte quality. In this study, a GnRH antagonist (Cetrotide) was used to suppress LH secretion during follicular differentiation to get a better insight into the physiological importance of the LH support during that period. Oocytes were collected by OPU and quality was assessed by measuring the blastocyst formation rate obtained after IVM-IVF. The oocyte transcriptome from GnRH antagonist-treated animals was also compared with that from a control group (coasting duration of 68 hours) to detect possible alterations at the mRNA level. The oocyte quality was not statistically affected by the treatment as shown by the blastocyst formation rate obtained. However, microarray analysis showed that a total of 226 genes had a significant difference (fold change >2, P <0.05) at the mRNA level, with the majority being in over-abundance in the treated group. Many genes related to RNA post-transcriptional modifications presented different abundance at the mRNA level significant differences in the control group (68 hrs), while translation function appeared to be affected, with many genes related to structural constituents of the ribosome presenting an over-abundance in the GnRH antagonist-treated group. Specific mRNAs with crucial roles in chromosome segregation control also showed significant difference at the mRNA level following Cetrotide treatment. The results presented here indicated that the suppression of the LH secretion in an optimal stimulated context would have an impact on the oocyte, with the possible alteration of critical functions related to translation capacity and chromosome segregation control.Theriogenology 05/2014; DOI:10.1016/j.theriogenology.2014.01.037 · 1.85 Impact Factor
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ABSTRACT: The hPrp19-CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. In order to elucidate the molecular architecture of the hPrp19-CDC5L complex, the crystal structure of CTNNBL1, one of the major components of this complex, was determined. Unlike canonical ARM-repeat proteins such as β-catenin and importin-α, CTNNBL1 was found to contain a twisted and extended ARM-repeat structure at the C-terminal domain and, more importantly, the protein formed a stable dimer. A highly negatively charged patch formed in the N-terminal ARM-repeat domain of CTNNBL1 provides a binding site for CDC5L, a binding partner of the protein in the hPrp19-CDC5L complex, and these two proteins form a complex with a stoichiometry of 2:2. These findings not only present the crystal structure of a novel ARM-repeat protein, CTNNBL1, but also provide insights into the detailed molecular architecture of the hPrp19-CDC5L complex.Acta Crystallographica Section D Biological Crystallography 03/2014; 70(Pt 3):780-8. DOI:10.1107/S139900471303318X · 7.23 Impact Factor