Correction to: Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment.

An amendment to this paper has been published and can be accessed via the original article.

Extensive rewiring and complex evolutionary dynamics in a C. elegans multiparameter transcription factor network.

Gene duplication results in two identical paralogs that diverge through mutation, leading to loss or gain of interactions with other biomolecules. Here, we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks.

Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment.

Background: GAD65 (Glutamic acid decarboxylase 65 KDa isoform) is one of the most important auto-antigens involved in Type 1 diabetes induction. Although it serves as one of the first injury markers of β-islets, the mechanisms governing GAD65 expression remain poorly understood. Since the regulation of GAD65 is crucial for the proper functioning of insulin secreting cells, we investigated the stress induced regulation of GAD65 transcription.

Enhanced yeast one-hybrid assays for high-throughput gene-centered regulatory network mapping.

A major challenge in systems biology is to understand the gene regulatory networks that drive development, physiology and pathology. Interactions between transcription factors and regulatory genomic regions provide the first level of gene control. Gateway-compatible yeast one-hybrid (Y1H) assays present a convenient method to identify and characterize the repertoire of transcription factors that can bind a DNA sequence of interest.

Heat-shock protein 70 binds to a novel sequence in 5' UTR of tumor suppressor SMAR1 and regulates its mRNA stability upon Prostaglandin A2 treatment.

Here, we report Prostaglandin A2 (PGA2) induced binding of HSP70 to a novel site on phi1 SMAR1 5' UTR which stabilizes the wild type transcript and leads to subsequent increase in SMAR1 protein levels. SMAR1 mediated cell cycle arrest is perturbed in PGA2-treated cells when HSP70 is knocked-down. Contrarily HSP70, unlike SMAR1, is overexpressed in breast cancers.

Nuclear matrix protein SMAR1 represses HIV-1 LTR mediated transcription through chromatin remodeling.

Nuclear Matrix and MARs have been implicated in the transcriptional regulation of host as well as viral genes but their precise role in HIV-1 transcription remains unclear. Here, we show that >98% of HIV sequences contain consensus MAR element in their promoter. We show that SMAR1 binds to the LTR MAR and reinforces transcriptional silencing by tethering the LTR MAR to nuclear matrix.

SMAR1 regulates free radical stress through modulation of AKR1a4 enzyme activity.

Tumor suppressor SMAR1 is known to be involved in regulation of cell cycle and apoptotic genes transcription. It also directly interacts and stabilizes p53 through phosphorylation at serine-15 residue. Although the functions of SMAR1 are mainly restricted to the nucleus, we report its novel function with the cytoplasm.

SMAR1 forms a ternary complex with p53-MDM2 and negatively regulates p53-mediated transcription.

The intra-cellular level of tumor suppressor protein p53 is tightly controlled by an autoregulatory feedback loop between the protein and its negative regulator MDM2. The role of MDM2 in down-regulating the p53 response in unstressed conditions and in the post-stress recovery phase is well documented. However, interplay between the N-terminal phosphorylations and C-terminal acetylations of p53 in this context remains unclear.

Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-beta-lactam.

We report herein the synthesis and biological evaluation of bile acid dimers linked through 1,2,3-triazole and bis-beta-lactam. The dimers were synthesized using 1,3-dipolar cycloaddition reaction of diazido bis-beta-lactams , and terminal alkynes derived from cholic acid/deoxycholic acid in the presence of Cu(i) catalyst (click chemistry). These novel molecules were evaluated in vitro for their antifungal and antibacterial activity.

Tumor suppressor SMAR1 downregulates Cytokeratin 8 expression by displacing p53 from its cognate site.

Intermediary filaments play a crucial role in transformation of cells to a malignant phenotype. Here, we report that tumor suppressor SMAR1 downregulates Cytokeratin 8 gene expression by modulating p53-mediated transactivation of this gene. Moreover, the cell surface cytokeratin expression was downregulated leading to a decreased migration and invasiveness of cells.

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents.

Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 microg/mL.

Stabilization of SMAR1 mRNA by PGA2 involves a stem loop structure in the 5' UTR.

Prostaglandins are anticancer agents known to inhibit tumor cell proliferation both in vitro and in vivo by affecting the mRNA stability. Here we report that a MAR-binding protein SMAR1 is a target of Prostaglandin A2 (PGA2) induced growth arrest. We identify a regulatory mechanism leading to stabilization of SMAR1 transcript.