Maintain stemness, commit to a specific lineage, differentiate, proliferate, or die. These are essential decisions that every cell is constantly challenged to make in multi-cellular organisms to ensure proper development, adult maintenance, and adaptability. SRY-related high-mobility-group box (Sox) transcription factors have emerged in the animal kingdom to help cells effect such decisions. They are encoded by twenty genes in humans and mice. They share a highly conserved high-mobilitygroup box domain that was originally identified in SRY, the sex-determining gene on the Y chromosome, and that has derived from a canonical high-mobility-group domain characteristic of chromatin-associated proteins. The high-mobility-group box domain binds DNA in the minor groove and increases its DNA binding affinity and specificity by interacting with many types of transcription factors. It also bends DNA and may thereby confer on Sox proteins a unique and critical role in the assembly of transcriptional enhanceosomes. Sox proteins fall into eight groups. Most feature a transactivation or transrepression domain and thereby also act as typical transcription factors. Each gene has distinct expression pattern and molecular properties, often redundant with those in the same group and overlapping with those in other groups. As a whole the Sox family controls cell fate and differentiation in a multitude of processes, such as male differentiation, stemness, neurogenesis, and skeletogenesis. We review their specific molecular properties and in vivo roles, stress recent advances in the field, and suggest directions for future investigations.

The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but the mode of action of the trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream of the Agc1 gene for aggrecan, a most essential cartilage proteoglycan and key marker of chondrocyte differentiation. This sequence directs expression of a minimal promoter in both embryonic and adult cartilage in transgenic mice, in a manner that matches Agc1 expression. The chondrogenic trio is required and sufficient to mediate the activity of this enhancer. It acts directly, Sox9 binding to a critical cis-acting element and L-Sox5/Sox6 binding to three additional elements, which are cooperatively needed. Upon binding to their specific sites, L-Sox5/Sox6 increases the efficiency of Sox9 binding to its own recognition site and thereby robustly potentiates the ability of Sox9 to activate the enhancer. L-Sox5/Sox6 similarly secures Sox9 binding to Col2a1 (encoding collagen-2) and other cartilage-specific enhancers. This study thus uncovers critical cis-acting elements and transcription factors driving Agc1 expression in cartilage and increases understanding of the mode of action of the chondrogenic Sox trio.

The Pti4, Pti5, and Pti6 proteins from tomato were identified based on their interaction with the product of the Pto disease resistance gene, a Ser-Thr protein kinase. They belong to the ethylene-response factor (ERF) family of plantunique transcription factors and bind specifically to the GCC-box cis element present in the promoters of many pathogenesis-related ( PR ) genes. Here, we show that these tomato ERFs are localized to the nucleus and function in vivo as transcription activators that regulate the expression of GCC box-containing PR genes. Expression of Pti4 , Pti5 , or Pti 6 in Arabidopsis activated the expression of the salicylic acid-regulated genes PR1 and PR2 . Expression of jasmonic acid-and ethylene-regulated genes, such as PR3 , PR4 , PDF1.2 , and Thi2.1 , was affected differently by each of the three tomato ERFs, with Arabidopsis -Pti4 plants having very high levels of PDF1.2 transcripts. Exogenous application of salicylic acid to Arabidopsis-Pti4 plants suppressed the increased expression of PDF1.2 but further stimulated PR1 expression. Arabidopsis plants expressing Pti4 displayed increased resistance to the fungal pathogen Erysiphe orontii and increased tolerance to the bacterial pathogen Pseudomonas syringae pv tomato . These results indicate that Pti4, Pti5, and Pti6 activate the expression of a wide array of PR genes and play important and distinct roles in plant defense. INTRODUCTIONPlants respond to pathogen attack by activating multiple defense mechanisms to protect themselves from infection. These rapid cellular responses often are triggered by the recognition of specific pathogens and the activation of highly regulated signal transduction pathways. A major target of these pathways is the cell nucleus, where signals lead to the transcriptional activation of a large array of defense genes (Maleck et al., 2000;Schenk et al., 2000). The products of these genes include pathogenesis-related (PR) proteins as well as enzymes involved in the biosynthesis of protective secondary metabolites. Although the functions of many PR proteins remain unknown, some PR proteins, such as ␤ -1,3-glucanase (PR2) and chitinase (PR3), are hydrolytic enzymes that have been shown to degrade fungal cell walls and to inhibit fungal growth both in vivo and in vitro (Broglie et al., 1991;Sela-Buurlage et al., 1993; Zhu et al., 1994). It was shown recently that osmotin (PR5) induces apoptosis in yeast, and it may act similarly toward plant fungal pathogens (Narasimhan et al., 2001).Several signaling molecules, such as salicylic acid (SA), ethylene (ET), and jasmonic acid (JA), have been shown to be important components of defense response pathways (Dong, 1998;Reymond and Farmer, 1998; Dempsey et al., 1999;Pieterse and van Loon, 1999). Infection by microbial pathogens results in an increase in the levels of these molecules in plants, and many PR genes that are induced upon pathogen infection also are upregulated by one or more of these signaling molecules (Malamy et al., 1990; Dempsey et al., 1999). The SA-dependent...

Summary Fleshy fruits are classically divided into climacteric and nonclimacteric types. It has long been thought that the ripening of climacteric and nonclimacteric fruits is regulated by ethylene and abscisic acid (ABA), respectively. Here, we report that sucrose functions as a signal in the ripening of strawberry (Fragaria × ananassa), a nonclimacteric fruit. Pharmacological experiments, as well as gain‐ and loss‐of‐function studies, were performed to demonstrate the critical role of sucrose in the regulation of fruit ripening. Fruit growth and development were closely correlated with a change in sucrose content. Exogenous sucrose and its nonmetabolizable analog, turanose, induced ABA accumulation in fruit and accelerated dramatically fruit ripening. A set of sucrose transporters, FaSUT1–7, was identified and characterized, among which FaSUT1 was found to be a major component responsible for sucrose accumulation during fruit development. RNA interference‐induced silencing of FaSUT1 led to a decrease in both sucrose and ABA content, and arrested fruit ripening. By contrast, overexpression of FaSUT1 led to an increase in both sucrose and ABA content, and accelerated fruit ripening. In conclusion, this study demonstrates that sucrose is an important signal in the regulation of strawberry fruit ripening.

Bud dormancy transition is a vital developmental process for perennial plant survival. The process is precisely regulated by diverse endogenous genetic factors and environmental cues, but the mechanisms are not yet fully understood. Prunus mume is an ideal crop for bud dormancy analysis because of its early spring-flowering characteristics and small sequenced genome. Here, we analyzed the transcriptome profiles at the three endodormancy stages and natural flush stage using RNA sequencing combined with phytohormone and sugar content measurements. Significant alterations in hormone contents and carbohydrate metabolism have been observed, and α-amylases, Glucan Hydrolase Family 17 and diphosphate-glycosyltransferase family might play crucial roles in the interactions between hormones and sugars. The following hypothetical model for understanding the molecular mechanism of bud dormancy in Prunus mume is proposed: low temperatures exposure induces the significant up-regulation of eight C-repeat binding factor genes, which directly promotes all six dormancy-associated MADS-box genes, resulting in dormancy establishment. The prolonged cold and/or subsequently increasing temperature then decreases the expression levels of these two gene families, which alleviates the inhibition of FLOWERING LOCUS T and reopens the growth-promoting pathway, resulting in dormancy release and the initiation of the bud break process.

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The papain-like protease of severe acute respiratory syndrome coronavirus (PLpro) (EC 3.4.22.46) is essential for the viral life cycle and therefore represents an important antiviral target. We have identified 6MP and 6TG as reversible and slow-binding inhibitors of SARS-CoV PLpro, which is the first report about small molecule reversible inhibitors of PLpro. The inhibition mechanism was investigated by kinetic measurements and computer docking. Both compounds are competitive, selective, and reversible inhibitors of the PLpro with K(is) values approximately 10 to 20 microM. A structure-function relationship study has identified the thiocarbonyl moiety of 6MP or 6TG as the active pharmacophore essential for these inhibitions, which has not been reported before. The inhibition is selective because these compounds do not exert significant inhibitory effects against other cysteine proteases, including SARS-CoV 3CLpro and several cathepsins. Thus, our results present the first potential chemical leads against SARS-CoV PLpro, which might be used as lead compounds for further optimization to enhance their potency against SARS-CoV. Both 6MP and 6TG are still used extensively in clinics, especially for children with acute lymphoblastic or myeloblastic leukemia. In light of the possible inhibition against subset of cysteine proteases, our study has emphasized the importance to study in depth these drug actions in vivo.

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