Zhao G, etal., J Exp Clin Cancer Res. 2015 Jun 24;34:66. doi: 10.1186/s13046-015-0177-y.
BACKGROUND: The Yin Yang 1 (YY1) transcription factor has been identified to target a plethora of potential target genes, which are important for cell proliferation and differentiation. Although the role that YY1 plays in different human types of cancer has been reported, its biological and mechani
stic significance in melanoma has not been well defined. METHODS: Quantitative RT-PCR analysis was used to determine whether aberrant YY1 and miR-9 expression occurred in melanoma, compared with benign nevi and normal tissue controls. Furthermore, the transcriptional regulation of YY1 on miR-9 expression was assessed by using quantitative ChIP-PCR assay. Subsequently, the effects of YY1 and miR-9 on proliferation, cell cycle, migration and invasion of melanoma cells were detected using CCK-8, flow cytometric analysis, wound healing and transwell invasion assays, respectively. Finally, the post-transcriptional regulation of miR-9 on RYBP was analyzed using luciferase reporter and immunoblot analysis. RESULTS: Elevated YY1 levels were observed in patients with melanoma, compared with benign nevi and normal tissue controls, and the increased YY1 was associated with melanoma metastasis state and tumor stage. Furthermore, YY1 negatively regulated miR-9 transcription. Silencing of YY1 inhibited proliferation, cell cycle progression, migration and invasion in melanoma cells, while ectopic of miR-9 did the same. Additionally, RYBP was shown to be a direct target of miR-9 through binding to its 3' UTR, thus forming a YY1 ~ miR-9 ~ RYBP axis. CONCLUSIONS: These results identify a novel YY1 ~ miR-9 ~ RYBP axis involved in melanoma tumorigenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms.
Cales C, etal., Mol Cell Biol. 2015 Dec 28;36(6):900-12. doi: 10.1128/MCB.00869-15.
Polycomb chromatin modifiers regulate hematopoietic pluripotent stem and progenitor cell self-renewal and expansion. Polycomb complex redundancy and biochemical heterogeneity complicate the unraveling of the functional contributions of distinct components. We have studied the hematopoietic activity
of RYBP, a direct interactor and proposed modulator of RING1A/RING1B-dependent histone H2A monoubiquitylation (H2AUb). Using a mouse model to conditionally inactivate Rybp in adult hematopoiesis, we have found that RYBP deletion results in a reversion of B-1-to-B-2 B-cell progenitor ratios, i.e., of the innate (predominantly fetal) to acquired (mostly adult) immunity precursors. Increased numbers of B-1 progenitors correlated with a loss of pre-proB cells, the B-2 progenitors. RYBP-deficient stem and progenitor cell populations (LKS) and isolated common lymphoid progenitors (CLP) gave rise to increased numbers of B-1 progenitors in vitro. Rybp inactivation, however, did not result in changes of global H2AUb and did not interact genetically with Ring1A or Ring1B deletions. These results show that a sustained regulation of the B-1-to-B-2 switch is needed throughout adult life and that RYBP plays an important role in keeping B-2 dominance, most likely independently of its Polycomb affiliation.
Ring1 and YY1 Binding Protein (RYBP) induces tumor-specific cell apoptosis, but the underlying molecular mechanism has not been fully understood. Here we conducted a yeast two hybrid screen and identified FANK1 (Fibronectin type III and ankyrin repeat domains 1)
as a novel RYBP-interacting protein. This interaction was confirmed by coimmunoprecipitation, GST pulldown and immunofluorescence assays. We mapped that the FNIII domain at the N-terminal of FANK1 binds to the Serine/Threonine-rich region at the C-terminal of RYBP. Further studies showed that overexpression of RYBP stabilized, whereas knockdown of RYBP by its specific shRNAs reduced, the expression of FANK1. Mechanistic studies revealed that RYBP inhibited the proteasome degradation of polyubiquitinated FANK1, thus prolonging the half-life of FANK1 protein. Functional studies indicated that RYBP activates FANK1-mediated activator protein 1 (AP-1) signaling pathway which contributes to tumor cell apoptosis. Taken together, our current study uncovered a new mechanism which RYBP utilizes to exert its pro-apoptotic activity in human tumor cells.
