HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and viability

The molecular basis of human papillomavirus (HPV)-mediated cellular immortalization and malignant transformation has illustrated an indispensable role of viral E6/E7-oncoproteins. However, the impact of viral-oncoproteins on the metabolic phenotype of cancer cells remains ambiguous. We showed silenc...

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Bibliographic Details
Published in:Virusdisease 2022-09, Vol.33 (3), p.223-235
Main Authors: Prakasam, Gopinath, Iqbal, Mohammad Askandar, Srivastava, Anusha, Bamezai, Rameshwar N. K., Singh, Rajnish Kumar
Format: Article
Language:English
Subjects:
Alternative splicing
Biochemistry
Biomedical and Life Sciences
c-Myc protein
Cell Biology
Cell cycle
Cell division
Cell proliferation
Cervical cancer
Dehydrogenases
Enzymes
Genes
Glucose
Glycerol
Glycolysis
Human papillomavirus
Immortalization
Kinases
Life Sciences
Metabolism
Microbiology
mRNA
Mutation
Myc protein
Oncoproteins
Original
Original Article
Phenotypes
Proteasomes
Protein Structure
Proteins
Pyruvate kinase
Pyruvic acid
Tumors
Viruses
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Summary:The molecular basis of human papillomavirus (HPV)-mediated cellular immortalization and malignant transformation has illustrated an indispensable role of viral E6/E7-oncoproteins. However, the impact of viral-oncoproteins on the metabolic phenotype of cancer cells remains ambiguous. We showed silencing of HPV18-encoded E6/E7-oncoprotein significantly reduced glucose consumption, lactate production, ATP level and viability. Silencing of HPV18-encoded E6/E7 in HeLa cells significantly down-regulated expression and activity of HK1, HK2, LDHA, and LDHB. Interestingly, there was an increased pyruvate kinase activity due to switch in expression from PKM2 isoform to PKM1. The switch in favor of alternatively spliced isoform PKM1, was regulated by viral-E6/E7-oncoprotein by inhibiting the c-Myc/hnRNP-axis. Further, the near absence of the PKM1 protein despite an adequate amount of PKM1 mRNA in HeLa cells was due to its proteasomal degradation. Our results suggests HPV18-encoded E6/E7 driven preferential expression of PKM2 is essential to support aerobic glycolysis and cell proliferation.
ISSN:2347-3584
2347-3517
DOI:10.1007/s13337-022-00776-w