The gene encoding ‘deleted in breast cancer 2’ (DBC2), also referred to as RHOBTB2 (Rho-related BTB domain-containing protein 2), is classified as a tumor suppressor gene. DBC2 is a substrate-specific adaptor protein for a novel class of Cullin-3 (CUL3)-based E3 ubiquitin ligases; however, it is unclear if the substrate adaptor function of DBC2 is required for its tumor suppressor activity. Furthermore, the key substrates of DBC2-mediated ubiquitination have yet to be identified. In the present study, we established a genome-wide human cDNA library-based in vitro ubiquitination target screening assay and identified Musashi-2 (MSI2) as a novel ubiquitination target protein of DBC2. MSI2 directly interacted with DBC2, and this interaction promoted MSI2 polyubiquitination and proteasomal degradation in breast cancer cells. Overexpression and knockdown experiments demonstrated that DBC2 suppressed MSI2-associated oncogenic functions and induced apoptosis. Immunohistochemistry analysis of a breast cancer tissue microarray revealed that DBC2 and MSI2 protein levels are inversely correlated in both normal breast tissues and breast cancer tissues. Taken together, these findings provide evidence that DBC2 suppresses tumorigenesis in breast cancer by ubiquitinating MSI2.

Accumulating evidence indicates that reactive oxygen species (ROS) are an important etiological factor for the induction of dermal papilla cell senescence and hair loss, which is also known alopecia. Arctiin is an active lignin isolated from Arctium lappa and has anti-inflammation, anti-microbial, and anti-carcinogenic effects. In the present study, we found that arctiin exerts anti-oxidative effects on human hair dermal papilla cells (HHDPCs). To better understand the mechanism, we analyzed the level of hydrogen peroxide (H₂O₂)-induced cytotoxicity, cell death, ROS production and senescence after arctiin pretreatment of HHDPCs. The results showed that arctiin pretreatment significantly inhibited the H₂O₂-induced reduction in cell viability. Moreover, H₂O₂-induced sub-G1 phase accumulation and G2 cell cycle arrest were also downregulated by arctiin pretreatment. Interestingly, the increase in intracellular ROS mediated by H₂O₂ was drastically decreased in HHDPCs cultured in the presence of arctiin. This effect was confirmed by senescence associated-beta galactosidase (SA-β-gal) assay results; we found that arctiin pretreatment impaired H₂O₂-induced senescence in HHDPCs. Using microRNA (miRNA) microarray and bioinformatic analysis, we showed that this anti-oxidative effect of arctiin in HHDPCs was related with mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. Taken together, our data suggest that arctiin has a protective effect on ROS-induced cell dysfunction in HHDPCs and may therefore be useful for alopecia prevention and treatment strategies.

Acne vulgaris is a common inflammatory skin disease, affecting adolescents across the globe. Recent evidences underline that Propionibacterium acnes (P. acnes) promotes acne through Toll-like receptor (TLR) activation. Especially, Toll-like receptor 2 (TLR2) has emerged as one of the major classes of pattern recognition receptors (PRRs) that are recognizing P. acnes in the epidermis and responsible for inflammation. Although P. acnes has been known to be one of the major causes of acne vulgaris, an appropriate drug to alleviate acne pathogenesis is poorly developed. This review focuses on the molecular structure of TLR2 as well as mechanism how TLR2 recognize P. acnes to induce inflammatory cytokines, which is related to acne vulgaris pathogenesis. Rigorous study about P. acnes mediated by TLR2 activation may provide insight into novel therapeutic targets of acne vulgaris.

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