Plants are capable of producing a wide variety of secondary metabolites which have a diverse range of functions that can be exploited for medicinal purposes; for example, paclitaxel is a major anti-cancer drug found in the bark of Taxus spp. There are however supply issues as the compound is only found at low concentrations (0.05%) within the plant. The complex paclitaxel biosynthetic pathway makes chemical synthesis non-commercially viable; therefore alternative biotechnological sources have been explored for production including heterologous expression systems and plant cell culture.
The absence of a lesion in the LEEP specimen is very common. A negative LEEP is associated with a persistence/recurrence rate similar to that of positive LEEP. We recommend that the follow-up for patients with no lesion in the LEEP specimen should be the same as that for patients with a lesion.
Flavonol
synthase (FLS) belongs to the 2-oxoglutarate-dependent dioxygenase
(2-ODD) superfamily. We isolated OsFLS from the rice
(Oryza sativa) cultivar “Ilmi” OsFLS
includes highly conserved 2-ODD-specific motifs and FLS-specific regions.
Recombinant OsFLS exhibited both FLS and flavanone 3β-hydroxylase
(F3H) activities, converting dihydroflavonols into flavonols and flavanones
into dihydroflavonols, respectively, and more efficiently used dihydrokaempferol
than dihydroquercetin as a substrate. OsFLS was expressed
in both nonpigmented and pigmented rice seeds and was developmentally
regulated during seed maturation. Transgenic tobacco (Nicotiana
tabacum) plants expressing OsFLS produced
pale pink or white flowers with significantly increased levels of
kaempferol-3-O-rutinoside and dramatically reduced
levels of anthocyanin in their petals. Additionally, pod size and
weight were reduced compared to the wild type. Several early and late
biosynthetic genes of flavonoid were downregulated in the transgenic
flowers. We demonstrated that OsFLS is a bifunctional 2-ODD enzyme
and functions in flavonol production in planta.
Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments, highlighting the need for therapeutic targets and predictive biomarkers. Here, we report a unique role for Bcl-2-associated athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme. Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis by increasing the intracellular mature form of cathepsin B, whereas BAG2 expression induces metastasis by blocking the auto-cleavage processing of pro-cathepsin B via interaction with the propeptide region. BAG2 regulates pro-cathepsin B/annexin II complex formation and facilitates the trafficking of pro-cathespin-B-containing TGN38-positive vesicles toward the cell periphery, leading to the secretion of pro-cathepsin B, which induces metastasis. Collectively, our results uncover BAG2 as a regulator of the oncogenic function of pro-cathepsin B and a potential diagnostic and therapeutic target that may reduce the burden of metastatic breast cancer.
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