2 resultados para BCL-2 FAMILY MEMBERS
em Duke University
Resumo:
BACKGROUND: In light of evidence showing reduced criminal recidivism and cost savings, adult drug treatment courts have grown in popularity. However, the potential spillover benefits to family members are understudied. OBJECTIVES: To examine: (1) the overlap between parents who were convicted of a substance-related offense and their children's involvement with child protective services (CPS); and (2) whether parental participation in an adult drug treatment court program reduces children's risk for CPS involvement. METHODS: Administrative data from North Carolina courts, birth records, and social services were linked at the child level. First, children of parents convicted of a substance-related offense were matched to (a) children of parents convicted of a nonsubstance-related offense and (b) those not convicted of any offense. Second, we compared children of parents who completed a DTC program with children of parents who were referred but did not enroll, who enrolled for <90 days but did not complete, and who enrolled for 90+ days but did not complete. Multivariate logistic regression was used to model group differences in the odds of being reported to CPS in the 1 to 3 years following parental criminal conviction or, alternatively, being referred to a DTC program. RESULTS: Children of parents convicted of a substance-related offense were at greater risk of CPS involvement than children whose parents were not convicted of any charge, but DTC participation did not mitigate this risk. Conclusion/Importance: The role of specialty courts as a strategy for reducing children's risk of maltreatment should be further explored.
Resumo:
Post-transcriptional regulation of cytoplasmic mRNAs is an efficient mechanism of regulating the amounts of active protein within a eukaryotic cell. RNA sequence elements located in the untranslated regions of mRNAs can influence transcript degradation or translation through associations with RNA-binding proteins. Tristetraprolin (TTP) is the best known member of a family of CCCH zinc finger proteins that targets adenosine-uridine rich element (ARE) binding sites in the 3’ untranslated regions (UTRs) of mRNAs, promoting transcript deadenylation through the recruitment of deadenylases. More specifically, TTP has been shown to bind AREs located in the 3’-UTRs of transcripts with known roles in the inflammatory response. The mRNA-binding region of the protein is the highly conserved CCCH tandem zinc finger (TZF) domain. The synthetic TTP TZF domain has been shown to bind with high affinity to the 13-mer sequence of UUUUAUUUAUUUU. However, the binding affinities of full-length TTP family members to the same sequence and its variants are unknown. Furthermore, the distance needed between two overlapping or neighboring UUAUUUAUU 9-mers for tandem binding events of a full-length TTP family member to a target transcript has not been explored. To address these questions, we recombinantly expressed and purified the full-length C. albicans TTP family member Zfs1. Using full-length Zfs1, tagged at the N-terminus with maltose binding protein (MBP), we determined the binding affinities of the protein to the optimal TTP binding sequence, UUAUUUAUU. Fluorescence anisotropy experiments determined that the binding affinities of MBP-Zfs1 to non-canonical AREs were influenced by ionic buffer strength, suggesting that transcript selectivity may be affected by intracellular conditions. Furthermore, electrophoretic mobility shift assays (EMSAs) revealed that separation of two core AUUUA sequences by two uridines is sufficient for tandem binding of MBP-Zfs1. Finally, we found evidence for tandem binding of MBP-Zfs1 to a 27-base RNA oligonucleotide containing only a single ARE-binding site, and showed that this was concentration and RNA length dependent; this phenomenon had not been seen previously. These data suggest that the association of the TTP TZF domain and the TZF domains of other species, to ARE-binding sites is highly conserved. Domains outside of the TZF domain may mediate transcript selectivity in changing cellular conditions, and promote protein-RNA interactions not associated with the ARE-binding TZF domain.
In summary, the evidence presented here suggests that Zfs1-mediated decay of mRNA targets may require additional interactions, in addition to ARE-TZF domain associations, to promote transcript destabilization and degradation. These studies further our understanding of post-transcriptional steps in gene regulation.