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Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1), attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

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14-Deoxy-11,12-didehydroandrographolide is a biologically active molecule present in the extract of Andrographis paniculata (Kalmegh), a classic ethnic herbal formula, which has been used for over thousand years as therapeutics to treat numerous infectious diseases like upper respiratory tract infection, urinary tract infection, and many more health issues. The present study is designed to ascertain an inhibitor against biofilm formation from the major metabolites of Andrographis paniculata, because the extract of this herb shows inhibition of bacterial quorum sensing (QS) communication and biofilm development against microorganisms. 14-Deoxy-11,12-didehydroandrographolide at 0.1 mM (sub-MIC dose) with azithromycin (6 μg/mL, sub-MIC) or gentamicin (4 μg/mL, sub-MIC) synergistically inhibits 92% biofilm production by a 48-h treatment against Pseudomonas aeruginosa. Further investigation carried out by atomic force microscopy shows promising reduction in roughness and height of biofilm in the presence of 14-deoxy-11,12-didehydroandrographolide compared with the control group. The content of extracellular polymeric substances, level of pyocyanin production, and synthesis of extracellular protease by P. aeruginosa have also been reduced significantly at around 90% in 14-deoxy-11,12-didehydroandrographolide-treated group. In conclusion, 14deoxy-11,12-didehydroandrographolide could be used as a drug molecule against biofilm development by inhibiting QS pathway in Pseudomonas aeruginosa.