The family of Poly(A)-binding proteins (PABPs) regulates the stability and translation of messenger RNAs (mRNAs). Here we reported that the three members of PABPs, including PABPC1, PABPC3 and PABPC4, were identified as novel substrates for MKRN3, whose deletion or loss-of-function mutations were genetically associated with human central precocious puberty (CPP). MKRN3-mediated ubiquitination was found to attenuate the binding of PABPs to the poly(A) tails of mRNA, which led to shortened poly(A) tail-length of GNRH1 mRNA and compromised the formation of translation initiation complex (TIC). Recently, we have shown that MKRN3 epigenetically regulates the transcription of GNRH1 through conjugating poly-Ub chains onto methyl-DNA bind protein 3 (MBD3). Therefore, MKRN3-mediated ubiquitin signalling could control both transcriptional and post-transcriptional switches of mammalian puberty initiation. While identifying MKRN3 as a novel tissue-specific translational regulator, our work also provided new mechanistic insights into the etiology of MKRN3 dysfunction-associated human CPP.
A large amount of differentially expressed proteins (DEPs) have been identified in various cancer proteomics experiments, curation and annotation of these proteins are important in deciphering their roles in oncogenesis and tumor progression, and may further help to discover potential protein biomarkers for clinical applications. In 2009, we published the first database of DEPs in human cancers (dbDEPCs). In this updated version of 2011, dbDEPC 2.0 has more than doubly expanded to over 4000 protein entries, curated from 331 experiments across 20 types of human cancers. This resource allows researchers to search whether their interested proteins have been reported changing in certain cancers, to compare their own proteomic discovery with previous studies, to picture selected protein expression heatmap across multiple cancers and to relate protein expression changes with aberrance in other genetic level. New important developments include addition of experiment design information, advanced filter tools for customer-specified analysis and a network analysis tool. We expect dbDEPC 2.0 to be a much more powerful tool than it was in its first release and can serve as reference to both proteomics and cancer researchers. dbDEPC 2.0 is available at http://lifecenter.sgst.cn/dbdepc/index.do.
Identification and annotation of the mutations involved in oncogenesis and tumor progression are crucial for both cancer biology and clinical applications. Previously, we developed a public resource CanProVar, a human cancer proteome variation database for storing and querying single amino acid alterations in the human cancers. Since the publication of CanProVar, extensive cancer genomics efforts have revealed the enormous genomic complexity of various types of human cancers. Thus, there is an overwhelming need for comprehensive annotation of the genomic alterations at the protein level and making such knowledge easily accessible. Here, we describe CanProVar 2.0, a significantly expanded version of CanProVar, in which the amount of cancer-related variations and non-cancer specific variations was increased by about ten folds as compared to the previous version. To facilitate the interpretation of the variations, we added to the database functional data on potential impact of the crVARs on 3D protein interaction and on the differential expression of the variant-bearing proteins between cancer and normal samples. The web interface allows for flexible queries based on gene or protein IDs, cancer types, chromosome locations, or pathways. An integrated protein sequence databases containing variations that can be directly used for proteomics database searching can be downloaded.
The
fully biobased flame retardant, which is based on the green
and convenient ionic reaction of phytic acid (PA) and taurine (TA)
in water, brings flame retardancy to polylactic acid (PLA) efficiently.
PLA composite passes UL-94 V-0 rating in vertical combustion successively
with only 0.5 wt % reactant of PA and TA (PA-TA). Moreover, the peak
heat release rate (PHRR) and the total heat release rate (THR) of
PLA composite are reduced by 13.1 and 10.0% with 5.0 wt % PA-TA. Moreover,
the elongation at break of PLA with 5.0 wt % PA-TA is 92.7% higher
than that of pure PLA due to the ultralow addition and the interaction
of hydrogen bonds between the flame retardant and the matrix material.
The resultant fully biodegradable flame-retardant PLA composites reported
here could be widely applied in electronic appliances, automobiles,
and other fields.
Porcine circovirus-like virus (PCLV) is a type of circular Rep-encoding single-stranded DNA virus and may be associated with the development of diarrheal symptoms in pigs. In this study, we retrospectively analyzed three years of past cases in Anhui, China, and reported a case of hemorrhagic enteritis and death in a pregnant sow possibly caused by PCLV. In addition, we analyzed the evolutionary characteristics of PCLV and found that mutation, recombination and selective pressure all played an important role in the evolution of PCLV. We identified N15D and T17S as well as L56T, T58R, K59Q, M62R, L75I and R190K mutations in two different branches, and we noted recombination events in the Rep of a group of Chinese strains. Analysis of selection pressure revealed that PCLV gained more positive selection, indicating that the virus is in a continuous evolutionary state. The PR2 plot, ENC-plot and neutrality analysis showed a greater role of natural selection than that of mutational pressure in the formation of codon usage patterns. This study is the first to identify PCLV in sows with hemorrhagic dysentery and death, and it provides new epidemiological information on PCLV infection in pigs in China.
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