A crucial role for the ubiquitously expressed transcription factor Sp1 at early stages of hematopoietic specification

ABSTRACT Claudins (CLDN) are a family of proteins that represent the most important components of tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between epithelial cells. Several types of viruses make full use of CLDN to facilitate entry into cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry. In this study, we found that CLDN4 functions as an anti-PRRSV factor by blocking its absorption during the early stages of infection. The small extracellular loop (ECL2) of CLDN4 restricted the viral particles outside cells by binding to GP3. A novel function of GP3-mediated regulation of CLDN4 transcription was suggested. CLDN4 can be decreased through downregulating the level of CLDN4 transcription by ubiquitinating the transcription factor, SP1. The mechanism by which highly pathogenic PRRSV infects the epithelium was proposed. Importantly, ECL2 was found to block PRRSV absorption and infection and neutralize the virus. A more in-depth understanding of PRRSV infection is described, and novel therapeutic antiviral strategies are discussed. IMPORTANCE In the present study, the role of CLDN4 in PRRSV infection was studied. The results showed that CLDN4 blocked absorption into cells and restricted extracellular viral particles via the interaction between the CLDN4 small extracellular loop, ECL2, and the viral surface protein GP3. GP3 was found to downregulate CLDN4 through ubiquitination of the transcription factor SP1 to facilitate viral entry. The mechanism by which highly pathogenic PRRSV infects the epithelium is suggested. A novel function of GP3 in regulating gene transcription was discovered. Moreover, ECL2 could block PRRSV absorption and infection, as well as neutralizing the virus in the supernatant, which may lead to the development of novel therapeutic antiviral strategies.

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The transcription factor Sp1 plays a crucial role in dok-7 gene expression

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2011.04.020 ◽

2011 ◽

Vol 408 (2) ◽

pp. 293-299 ◽

Cited By ~ 5

Author(s):

Johko Hamuro ◽

Yukihiro Hishida ◽

Osamu Higuchi ◽

Yuji Yamanashi

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Crucial Role ◽

Transcription Factor Sp1

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Faculty Opinions recommendation of IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735902284.793562250 ◽

2019 ◽

Author(s):

Elisa Vicenzi

Keyword(s):

Transcription Factor ◽

Transcription Factor Sp1 ◽

Hiv 1

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SOG1 transcription factor promotes the onset of endoreduplication under salinity stress in Arabidopsis

Scientific Reports ◽

10.1038/s41598-021-91293-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kalyan Mahapatra ◽

Sujit Roy

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Transcription Factor ◽

Programmed Cell Death ◽

Salinity Stress ◽

Crucial Role ◽

Genome Stability ◽

Cell Cycle Checkpoint ◽

Cell Cycle Regulators

AbstractAs like in mammalian system, the DNA damage responsive cell cycle checkpoint functions play crucial role for maintenance of genome stability in plants through repairing of damages in DNA and induction of programmed cell death or endoreduplication by extensive regulation of progression of cell cycle. ATM and ATR (ATAXIA-TELANGIECTASIA-MUTATED and -RAD3-RELATED) function as sensor kinases and play key role in the transmission of DNA damage signals to the downstream components of cell cycle regulatory network. The plant-specific NAC domain family transcription factor SOG1 (SUPPRESSOR OF GAMMA RESPONSE 1) plays crucial role in transducing signals from both ATM and ATR in presence of double strand breaks (DSBs) in the genome and found to play crucial role in the regulation of key genes involved in cell cycle progression, DNA damage repair, endoreduplication and programmed cell death. Here we report that Arabidopsis exposed to high salinity shows generation of oxidative stress induced DSBs along with the concomitant induction of endoreduplication, displaying increased cell size and DNA ploidy level without any change in chromosome number. These responses were significantly prominent in SOG1 overexpression line than wild-type Arabidopsis, while sog1 mutant lines showed much compromised induction of endoreduplication under salinity stress. We have found that both ATM-SOG1 and ATR-SOG1 pathways are involved in the salinity mediated induction of endoreduplication. SOG1was found to promote G2-M phase arrest in Arabidopsis under salinity stress by downregulating the expression of the key cell cycle regulators, including CDKB1;1, CDKB2;1, and CYCB1;1, while upregulating the expression of WEE1 kinase, CCS52A and E2Fa, which act as important regulators for induction of endoreduplication. Our results suggest that Arabidopsis undergoes endoreduplicative cycle in response to salinity induced DSBs, showcasing an adaptive response in plants under salinity stress.

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