HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.

YAP/TAZ transcriptional co-activators play pivotal roles in tumorigenesis. In the Hippo pathway, diverse signals activate the MST-LATS kinase cascade that leads to YAP/TAZ phosphorylation, and subsequent ubiquitination and proteasomal degradation by SCFß-TrCP . When the MST-LATS kinase cascade is inactive, unphosphorylated or dephosphorylated YAP/TAZ translocate into the nucleus to mediate TEAD-dependent gene transcription. Hippo signaling-independent YAP/TAZ activation in human malignancies has also been observed, yet the mechanism remains largely elusive. Here, we report that the ubiquitin E3 ligase HERC3 can promote YAP/TAZ activation independently of its enzymatic activity. HERC3 directly binds to ß-TrCP, blocks its interaction with YAP/TAZ, and thus prevents YAP/TAZ ubiquitination and degradation. Expression levels of HERC3 correlate with YAP/TAZ protein levels and expression of YAP/TAZ target genes in breast tumor cells and tissues. Accordingly, knockdown of HERC3 expression ameliorates tumorigenesis of breast cancer cells. Our results establish HERC3 as a critical regulator of the YAP/TAZ stability and a potential therapeutic target for breast cancer.

The evolutionary origin and domestication history of goldfish (Carassius auratus).

Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild crucian carp revealed the origin of goldfish and identified genomic regions that have been shaped by selective sweeps linked to its domestication. Our comprehensive collection of goldfish varieties enabled us to associate genetic variations with a number of well-known anatomical features, including features that distinguish traditional goldfish clades. Additionally, we identified a tyrosine-protein kinase receptor as a candidate causal gene for the first well-known case of Mendelian inheritance in goldfish-the transparent mutant. The goldfish genome and diversity data offer unique resources to make goldfish a promising model for functional genomics, as well as domestication.

Genomics and transcriptomics reveal ß-carotene synthesis mechanism in Dunaliella salina.

Dunaliella salina is by far the most salt-tolerant organism and contains many active substances, including ß-carotene, glycerol, proteins, and vitamins, using in the production of dried biomass or cell extracts for the biofuels, pharmaceutical formulations, food additives, and fine chemicals, especially ß-carotene. We report a high-quality genome sequence of D. Salina FACHB435, which has a 472 Mb genome size, with a contig N50 of 458 Kb. A total of 30,752 protein-coding genes were predicted. The annotation results evaluated by BUSCO was shown that completeness was 91.0% and replication was 53.1%. The fragments were 6.3% and the deletions were 2.6%. Phylogenomic and comparative genomic analyses revealed that A. thaliana diverged from Volvocales about 448 million years ago, then Volvocales C. eustigma, D. salina, and other species diverged about 250 million years ago. High light could promote the accumulation of ß-carotene in D. salina at a 13 d stage of culture. The enrichment of DEGs in KEGG, it notes that the predicted up-regulated genes of carotenoid metabolic pathway include DsCrtB, DsPDS, DsZ-ISO, DsZDS, DsCRTISO, DsLUT5, DsCrtL-B, and DsCCD8, while the predicted down-regulated genes include DsCrtF, and DsLUT1. The four genes that were both up-regulated and down-regulated were DsZEP, DsCrtR-b, DsCruA/P and DsCrtZ 4. The research results can provide scientific basis for the industrialization practice of D. salina.