Autoregulation of DNA binding and protein stability of Kaposi's sarcoma-associated herpesvirus ORF50 protein

Journal of Virology
Pey-Jium Chang, George Miller

Abstract

A transcriptional activator encoded in open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) initiates the viral lytic cycle. ORF50 protein activates downstream KSHV target genes by at least two mechanisms: direct recognition of response elements in promoter DNA and interaction with cellular proteins bound to promoter DNA. We have identified a multifunctional regulatory region, present in amino acids (aa) 520 to 535 of ORF50 protein, that controls DNA binding and protein stability. Deletion of aa 521 to 534 or mutation of a basic motif (KKRK) in this regulatory region dramatically enhances DNA binding by ORF50 protein, as shown by electrophoretic mobility shift, DNA affinity chromatography, and chromatin immunoprecipitation assays. Deletion of the regulatory region and mutations in the KKRK motif also lead to abundant expression of an electrophoretic mobility variant, ORF50B, which appears to be a form of ORF50 protein that is decreased in posttranslational modification. Enhanced DNA binding and enhanced expression of ORF50B are independent phenomena. The regulatory region likely inhibits DNA binding through interactions with the DNA binding domain in aa 1 to 390 and destabilizes ORF50B through interac...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J Hagman, R Grosschedl
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J T Kadonaga, R Tjian
May 4, 1995·The New England Journal of Medicine·E CesarmanD M Knowles
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·J J RussoP S Moore
Aug 1, 1997·Journal of Virology·H W VirginS H Speck
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·R SunG Miller
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J GoudsmitG J Weverling
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Miles A Pufall, Barbara J Graves

❮ Previous
Next ❯

Citations

Jun 1, 2011·Advances in Virology·Fengchun YeShou-Jiang Gao
May 6, 2017·Frontiers in Microbiology·Kawalpreet K Aneja, Yan Yuan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.