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Several proteins participate in the initiation of DNA replication

Posted by star on 2018-08-22 19:57:19
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    Once oriC had been cloned it became possible to study the initiation of DNA replication in vitro. Arthur Kornberg and coworkers performed the difficult but rewarding task of purifying the enzymes that participate in the initiation process and elucidating their function. The first two stages in the replication initiation process, origin recognition and DNA unwinding, were described above. During the next stage, helicase loading, the DnaB helicase is loaded onto each of the single strands in the unwound AT-rich region of oriC. Both DnaC and DnaA·ATP participate in loading the DnaB hexamers. ATP hydrolysis leads to DnaC release, freeing each DnaB helicase to move in a 5'→3'direction and thereby extend the unwound region of oliC to about 65 nucleotides.

   

    Next, two DnaG (primase) molecules enter the complex one primase is associated with each DnaB helicase. Each primase then synthesizes a leading strand primer. Formation of these RNA primers ensures that replication begins exclusively at oriC and that a pair of replication forks is formed for bidirectional replication. primase has a zinc binding domain at its N-terminus, a Dna8 binding domain at its C-terminus, and an RNA polymerase domain in the middle. The final stage of the initiation cycle involves the addition of the sliding clamp and DNA polymerase Ⅲ holoenzyme (see below) with the concomitant release of DnaA · ADP from the DnaA boxes.




LHPP is a novel tumor suppressor protein that removes histidine-linked phosphate groups from proteins. LHPP inhibits tumors and maintains liver function: In healthy tissues, LHPP can be normally expressed. In patients with hepatocellular carcinoma, LHPP expression gradually decreases or even disappears as the cancer develops. Decreased levels of LHPP, increased histone phosphorylation of protein in the body, increased the activity of some proteins and activated related pathways, thereby inducing cancer and shortening the life expectancy of patients. LHPP is expected as a biomarker to assess the risk or progression of liver cancer in patients, and to change the status of liver cancer treatment. In addition, researchers have also found that LHPP is associated with oral cancer, throat cancer, and acute lymphoblastic leukemia.



A Novel Tumor Suppressor Protein-LHPP

Posted by star on 2018-08-22 19:04:48
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On March 21, 2018, a paper named “The protein histidine phosphatase LHPP is a tumour suppressor” published on the journal of Nature. In their study, they demonstrated that the loss of LHPP protein promoted tumor growth and reduced the chance of survival in cancer patients. LHPP may potentially serve as a prognostic biomarker.

By knocking out the PTEN and TSC1 genes and activating the mTOR signaling pathway, the researchers constructed an L-dKO mouse model that developed a macroscopic tumor at 16 weeks and developed liver cancer at 20 weeks. The results of the proteomic analysis showed that LHPP decreased slightly at 16 weeks and decreased significantly at 20 weeks in L-dKO mice. The researchers then did a further experiment which used adenoviral transfection and observed that injection of exogenous LHPP significantly inhibited the size and number of tumor cells at 20 weeks. From the clinical data, the researchers found that the survival of patients with low expression of LHPP was reduced by nearly 2 years. Using the TCGA and ICGC database, they also found that there were 49 LHPP mutation rates of 24.5% in a variety of cancers. These experimental results and clinical data all indicate that LHPP is a tumor suppressor gene.

With the further study of the mechanism of action of LHPP, they found that LHPP could remove the histidine-linked phosphate group in the protein. In the absence of LHPP, the histidine phosphorylation of the global protein increased, leading to the activation of several important functions and uncontrolled cell proliferation which promoted tumor growth and cancer.

Welcome to choose and buy the product LHPP protein, LHPP antibody or LHPP kit.



New hope for the treatment of liver disease

Posted by star on 2018-08-22 19:03:55
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SQLE is a rate-limiting enzyme for cholesterol biosynthesis in human. Nonalcoholic fatty liver disease (NAFLD)–induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world. RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase (SQLE) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. It is reported that SQLE expression is associated with poor survival of HCC patients. SQLE overexpression caused a more notable rise in cholesteryl esters and activated the PTEN/PI3K/AKT/mTOR signaling cascade to drive carcinogenesis in NAFLD-HCC cell lines。Cholesteryl esters were able to induce NAFLD-HCC cell growth. The data indicate that terbinafine(SQLE inhibitor), by inhibiting SQLE, suppressed the accumulation of liver cholesterol/cholesteryl ester and blocked the SQLE-ROS-DNMT3A-PTEN oncogenic axis, ultimately resulting in inhibition of hepatocarcinogenesis in Sqle transgenic mice. Pharmacological inhibition of SQLE is hence a promising approach that should be safe and effective for the prevention and treatment of NAFLD-HCC.



SARS coronavirus made new progress

Posted by star on 2018-08-22 01:56:24
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Recently, researchers found a natural gene bank of the bat SARS coronavirus in Yunnan, China. The study revealed that Chinese bats carry different strains of SARS-CoV that spread across the species to the human population, revealing the possible recombination of the SARS coronavirus Origin, for the prevention of related diseases provides an important basis.

Bat is a natural storage host for the SARS coronavirus. Since 2005, several research teams have found more and more SARS-CoVs in various Asteridae in different parts of the world. However, all currently reported bat SARS coronaviruses have diverged from the SARS coronavirus at least in two genes. Questions such as how SARS evolved in bats and where bat populations appear have not been answered.

The research team has conducted long-term surveillance of the SARS coronavirus from a cave-headed Chrysomeelidae population in Yunnan province since 2011, and SARS-CoV RNA was detected in 64 bat-pellets and anal swab samples. Analysis shows that the bat SARS coronavirus circulating in this cave is highly diverse.

The experts conducted a genetic analysis of 11 newly discovered SARS coronaviruses and conducted genome-wide sequence analysis of 15 strains found in this cave. The results showed that the bat SARS-CoV circulating in the cave was similar to each other in non-structural protein genes, and some of their genes showed extremely rich genetic diversity. The entire genome of the SARS coronavirus can be found in the natural gene library of the SARS coronavirus.

Through further recombination analysis, experts found frequent recombination evidence at multiple sites within these SARS-CoV genes and speculate that a direct ancestry of the SARS-CoV may occur through a series of episodes of ancestry of these bat SARS-CoVs Restructurings and produce.



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