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1.
Subcell Biochem ; 100: 269-336, 2022.
Article in English | MEDLINE | ID: mdl-36301498

ABSTRACT

Glucose metabolism plays a vital role in regulating cellular homeostasis as it acts as the central axis for energy metabolism, alteration in which may lead to serious consequences like metabolic disorders to life-threatening diseases like cancer. Malignant cells, on the other hand, help in tumor progression through abrupt cell proliferation by adapting to the changed metabolic milieu. Metabolic intermediates also vary from normal cells to cancerous ones to help the tumor manifestation. However, metabolic reprogramming is an important phenomenon of cells through which they try to maintain the balance between normal and carcinogenic outcomes. In this process, transcription factors and chromatin modifiers play an essential role to modify the chromatin landscape of important genes related directly or indirectly to metabolism. Our chapter surmises the importance of glucose metabolism and the role of metabolic intermediates in the cell. Also, we summarize the influence of histone effectors in reprogramming the cancer cell metabolism. An interesting aspect of this chapter includes the detailed methods to detect the aberrant metabolic flux, which can be instrumental for the therapeutic regimen of cancer.


Subject(s)
Glucose , Neoplasms , Humans , Glucose/metabolism , Glycolysis/genetics , Chromatin/genetics , Neoplasms/metabolism , Metabolic Networks and Pathways , Epigenesis, Genetic
2.
FEBS J ; 289(21): 6694-6713, 2022 11.
Article in English | MEDLINE | ID: mdl-35653238

ABSTRACT

Hepatitis B virus (HBV) is the leading cause of liver disease ranging from acute and chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Studies have revealed that HBV infection broadly reprogrammes the host cellular metabolic processes for viral pathogenesis. Previous reports have shown that glycolysis and gluconeogenesis are among the most deregulated pathways during HBV infection. We noted that despite being one of the rate-limiting enzymes of gluconeogenesis, the role and regulation of Fructose-1,6-bisphosphatase 1 (FBP1) during HBV infection is not much explored. In this study, we report FBP1 upregulation upon HBV infection and unravel a novel mechanism of epigenetic reprogramming of FBP1 by HBV via utilizing host factor Speckled 110 kDa (Sp110). Here, we identified acetylated lysine 18 of histone H3 (H3K18Ac) as a selective interactor of Sp110 Bromodomain. Furthermore, we found that Sp110 gets recruited on H3K18Ac-enriched FBP1 promoter, and facilitates recruitment of deacetylase Sirtuin 2 (SIRT2) on that site in the presence of HBV. SIRT2 in turn brings its interactor and transcriptional activator Hepatocyte nuclear factor 4-alpha to the promoter, which ultimately leads to a loss of DNA methylation near the cognate site. Interestingly, this Sp110 driven FBP1 regulation during infection was found to promote viral-borne HCC progression. Moreover, Sp110 can be used as a prognostic marker for the hepatitis-mediated HCC patients, where high Sp110 expression significantly lowered their survival. Thus, the epigenetic reader protein Sp110 has potential to be a therapeutic target to challenge HBV-induced HCCs.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Epigenesis, Genetic , Fructose , Fructose-Bisphosphatase/genetics , Fructose-Bisphosphatase/metabolism , Hepatitis B/complications , Hepatitis B/genetics , Hepatitis B virus/genetics , Hepatitis B virus/metabolism , Hepatocyte Nuclear Factor 4/genetics , Liver Neoplasms/pathology , Sirtuin 2/metabolism
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