De-ubiquitination of SAMHD1 by USP7 overcomes oncogenic stress and contributes to chemotherapy insensitivity DOI Creative Commons
Jingwei Liu, Tingting Zhou, Xiang Da Dong

et al.

Research Square (Research Square), Journal Year: 2021, Volume and Issue: unknown

Published: Aug. 20, 2021

Abstract Oncogenic stress induces DNA damage response (DDR) that guards against genetic instability during the evolution of cancer. SAMHD1, a dNTPase protecting cells from viral infections, has been recently found to participate in repair process. However, its role tumorigenesis remains largely unknown. Here, we show SAMHD1 is up-regulated early-stage human carcinoma tissues and cell lines under oxidative or genotoxic insults. We further demonstrate de-ubiquitinating enzyme USP7 interacts with de-ubiquitinates it at lysine 421, thus stabilizing protein expression, promotes tumor survival stress. Furthermore, levels positively correlates various carcinomas, associated an unfavorable outcome patients who underwent chemotherapy. Moreover, inhibitor sensitizes chemotherapeutic agents by decreasing vitro vivo. These findings suggest targeting may help overcome chemoresistance, necessitating investigation pursuit precision medicine.

Language: Английский

Protein-protein interaction modulators: advances, successes and remaining challenges DOI
Lloyd Mabonga, Abidemi Paul Kappo

Biophysical Reviews, Journal Year: 2019, Volume and Issue: 11(4), P. 559 - 581

Published: July 12, 2019

Language: Английский

Citations

175
Sensor Sensibility—HIV-1 and the Innate Immune Response DOI Creative Commons
Xin Yin, Simon Langer, Zeli Zhang

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(1), P. 254 - 254

Published: Jan. 20, 2020

Innate immunity represents the human immune system's first line of defense against a pathogenic intruder and is initiated by recognition conserved molecular structures known as pathogen-associated patterns (PAMPs) specialized cellular sensors, called pattern receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) unique RNA that causes acquired syndrome (AIDS) in infected individuals. During replication cycle, HIV-1 undergoes reverse transcription its genome integrates resulting DNA into genome. Subsequently, integrated provirus results production new virions spreading infection virus. Throughout viral numerous nucleic acid derived PAMPs can be recognized diverse set innate sensors cells. However, has evolved efficient strategies to evade or counteract this surveillance downstream responses. Understanding underpinnings concerted actions system, well corresponding evasion mechanisms during infection, critical understanding transmission pathogenesis, may provide important guidance for design appropriate adjuvant vaccine strategies. Here, we summarize current knowledge basis sensing cells, including CD4+ T dendritic macrophages. Furthermore, discuss underlying which regulated, describe developed

Language: Английский

Citations

70
De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity DOI Creative Commons
Jingwei Liu, Tingting Zhou, Xiang Da Dong

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(22), P. 1843 - 1856

Published: April 20, 2023

Abstract Oncogenic stress induces DNA damage repair (DDR) that permits escape from mitotic catastrophe and allows early precursor lesions during the evolution of cancer. SAMHD1, a dNTPase protecting cells viral infections, has been recently found to participate in process. However, its role tumorigenesis remains largely unknown. Here, we show SAMHD1 is up-regulated early-stage human carcinoma tissues cell lines under oxidative or genotoxic insults. We further demonstrate de-ubiquitinating enzyme USP7 interacts with de-ubiquitinates it at lysine 421, thus stabilizing protein expression for interaction CtIP DDR, which promotes tumor survival stress. Furthermore, levels positively correlates various carcinomas, associated an unfavorable outcome patients who underwent chemotherapy. Moreover, inhibitor sensitizes chemotherapeutic agents by decreasing vitro vivo. These findings suggest de-ubiquitination DDR overcome oncogenic affect chemotherapy sensitivity.

Language: Английский

Citations

17
Interplay between Intrinsic and Innate Immunity during HIV Infection DOI Creative Commons

Louis Bergantz,

Frédéric Subra,

Eric Deprez

et al.

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 922 - 922

Published: Aug. 17, 2019

Restriction factors are antiviral components of intrinsic immunity which constitute a first line defense by blocking different steps the human immunodeficiency virus (HIV) replication cycle. In immune cells, HIV infection is also sensed several pattern recognition receptors (PRRs), leading to type I interferon (IFN-I) and inflammatory cytokines production that upregulate interferon-stimulated genes (ISGs). Several studies suggest link between these two types immunity. Indeed, restriction factors, generally interferon-inducible, able modulate responses. This review highlights recent knowledge interplay inducing defenses. Counteraction this innate viral proteins will be discussed.

Language: Английский

Citations

31
HIV-1 Latency: From Acquaintance to Confidant DOI Creative Commons

Chenbo Yang,

Ling Tong, Jing Xue

et al.

Journal of Virus Eradication, Journal Year: 2025, Volume and Issue: unknown, P. 100597 - 100597

Published: May 1, 2025

Citations

0
SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications DOI Creative Commons
Aiza Khan, Consolato Sergi

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 25, 2020

The recent outbreak of coronavirus infectious disease 2019 (COVID19) caused by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In past two previously similar CoVs, acute respiratory syndrome CoV (SARS‐CoV-1) Middle East (MERS‐CoV) also gained global attention as they produced clinical symptoms to those utilizing angiotensin-converting enzyme 2 (ACE2) receptor enter inside cells. COVID-19 may present with neurological symptoms. proper understanding expression distribution ACE2 central peripheral nerve systems is crucial understand better morbidity COVID-19. Using bioinformatic tool STRING references through text mining tools associated Coronaviruses, we identified SAMHD1 probable link Compared response influenza A virus syncytial virus, evokes a that lacks robust induction subset cytokines, including Type I III interferons well few chemokines. We correlate pathogenesis neurologic complications found links NF-κB pathway. No correlation was other molecules Coronavirus infection, ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, VPRBP. suggest molecule be behind mechanisms

Language: Английский

Citations

24
Tetraspanin CD81 regulates HSV-1 infection DOI Open Access
Beatriz Benayas, Isabel Sastre, Soraya López‐Martín

et al.

Medical Microbiology and Immunology, Journal Year: 2020, Volume and Issue: 209(4), P. 489 - 498

Published: June 4, 2020

Language: Английский

Citations

18
Regulation of Viral Restriction by Post-Translational Modifications DOI Creative Commons
Célia Chamontin, Guillaume Bossis, Sébastien Nisole

et al.

Viruses, Journal Year: 2021, Volume and Issue: 13(11), P. 2197 - 2197

Published: Nov. 1, 2021

Intrinsic immunity is orchestrated by a wide range of host cellular proteins called restriction factors. They have the capacity to interfere with viral replication, and most them are tightly regulated interferons (IFNs). In addition, their regulation through post-translational modifications (PTMs) constitutes major mechanism shape action positively or negatively. Following infection, factor modification can be decisive. Palmitoylation IFITM3, SUMOylation MxA, SAMHD1 TRIM5α glycosylation BST2 some those PTMs required for antiviral activity. Nonetheless, benefit manipulating machinery, viruses evolved sophisticated mechanisms counteract Indeed, many evade activity inducing ubiquitination subsequent degradation. Studies on substrates essential understanding defense provide global vision all possible regulations immune response at given time under specific infection conditions. Our aim was an overview current knowledge regarding role factors emphasis impact replication.

Language: Английский

Citations

15
Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels DOI Creative Commons
Moritz Schüssler, Kerstin Schott, Nina V. Fuchs

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(5)

Published: Oct. 6, 2023

We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of sterile α motif and HD domain-containing protein 1 (SAMHD1) T592 phosphorylation on anti-viral restriction control cellular dNTP levels endogenous, physiologically relevant context. A proper understanding mechanism function SAMHD1 will provide attractive strategies aiming at selectively manipulating without affecting other functions. Even more, our toolkit may inspire further genetic analysis investigation factors inhibiting retroviruses their regulation, leading a deeper intrinsic immunity.

Language: Английский

Citations

6
Elevation in viral entry genes and innate immunity compromise underlying increased infectivity and severity of COVID-19 in cancer patients DOI Creative Commons
Jennifer Kwan, Liang Lin, Rachel Bell

et al.

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Feb. 25, 2021

Abstract Multiple studies have reported a doubling in risk of Coronavirus Disease-2019 (COVID-19) among cancer patients. Here, we examine the potential biological rationale behind this recurrent epidemiological observation. By leveraging large-scale genome-wide transcriptional data normal and malignant tissues from adults children, found evidence increased expression SARS-CoV-2 viral entry genes state, particularly respiratory, gastrointestinal, genitourinary tract tissues, with decreased pediatric vs . adult samples. Additionally, by interrogating temporal effects radiotherapy on human peripheral blood mononuclear mucosal cells, observed important treatment-related alterations host innate immunity, specifically type I interferon responses. Overall, cancers enhance critical genes, defenses can be dysregulated transiently during radiation treatments. These factors may contribute to susceptibility severity COVID-19

Language: Английский

Citations

11