SUMOylation regulates the number and size of promyelocytic leukemia-nuclear bodies (PML-NBs) and arsenic perturbs SUMO dynamics on PML by insolubilizing PML in THP-1 cells

2022 ◽  
Author(s):  
Seishiro Hirano ◽  
Osamu Udagawa
Keyword(s):  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Promyelocytic Leukemia Nuclear Bodies

scholarly journals Dynamics of Telomeres and Promyelocytic Leukemia Nuclear Bodies in a Telomerase-negative Human Cell Line

2009 ◽  
Vol 20 (7) ◽  
pp. 2070-2082 ◽  
Author(s):  
Thibaud Jegou ◽  
Inn Chung ◽  
Gerrit Heuvelman ◽  
Malte Wachsmuth ◽  
Sabine M. Görisch ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Cell Line ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Nuclear Space ◽  
Telomere Repeat ◽  
Lac Operator ◽  
Alternative Lengthening ◽  
Promyelocytic Leukemia Nuclear Bodies ◽  
Negative Tumor

Telomerase-negative tumor cells maintain their telomeres via an alternative lengthening of telomeres (ALT) mechanism. This process involves the association of telomeres with promyelocytic leukemia nuclear bodies (PML-NBs). Here, the mobility of both telomeres and PML-NBs as well as their interactions were studied in human U2OS osteosarcoma cells, in which the ALT pathway is active. A U2OS cell line was constructed that had lac operator repeats stably integrated adjacent to the telomeres of chromosomes 6q, 11p, and 12q. By fluorescence microscopy of autofluorescent LacI repressor bound to the lacO arrays the telomere mobility during interphase was traced and correlated with the telomere repeat length. A confined diffusion model was derived that describes telomere dynamics in the nucleus on the time scale from seconds to hours. Two telomere groups were identified that differed with respect to the nuclear space accessible to them. Furthermore, translocations of PML-NBs relative to telomeres and their complexes with telomeres were evaluated. Based on these studies, a model is proposed in which the shortening of telomeres results in an increased mobility that could facilitate the formation of complexes between telomeres and PML-NBs.

scholarly journals Functional Reorganization of Promyelocytic Leukemia Nuclear Bodies during BK Virus Infection

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Mengxi Jiang ◽  
Pouya Entezami ◽  
Monica Gamez ◽  
Thomas Stamminger ◽  
Michael J. Imperiale
Keyword(s):  
Cellular Localization ◽  
Antiviral Treatment ◽  
Bk Virus ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Host Cells ◽  
Viral Dna ◽  
Transplant Patients ◽  
Complete Life Cycle ◽  
Promyelocytic Leukemia Nuclear Bodies

ABSTRACTBK virus (BKV) is the causative agent for polyomavirus-associated nephropathy, a severe disease found in renal transplant patients due to reactivation of a persistent BKV infection. BKV replication relies on the interactions of BKV with many nuclear components, and subnuclear structures such as promyelocytic leukemia nuclear bodies (PML-NBs) are known to play regulatory roles during a number of DNA virus infections. In this study, we investigated the relationship between PML-NBs and BKV during infection of primary human renal proximal tubule epithelial (RPTE) cells. While the levels of the major PML-NB protein components remained unchanged, BKV infection of RPTE cells resulted in dramatic alterations in both the number and the size of PML-NBs. Furthermore, two normally constitutive components of PML-NBs, Sp100 and hDaxx, became dispersed from PML-NBs. To define the viral factors responsible for this reorganization, we examined the cellular localization of the BKV large tumor antigen (TAg) and viral DNA. TAg colocalized with PML-NBs during early infection, while a number of BKV chromosomes were adjacent to PML-NBs during late infection. We demonstrated that TAg alone was not sufficient to reorganize PML-NBs and that active viral DNA replication is required. Knockdown of PML protein did not dramatically affect BKV growth in culture. BKV infection, however, was able to rescue the growth of an ICP0-null herpes simplex virus 1 mutant whose growth defect was partially due to its inability to disrupt PML-NBs. We hypothesize that the antiviral functions of PML-NBs are inactivated through reorganization during normal BKV infection.IMPORTANCEBK virus (BKV) is a human pathogen that causes severe diseases, including polyomavirus-associated nephropathy in kidney transplant patients and hemorrhagic cystitis in bone marrow transplant recipients. How BKV replication is regulated and the effects of a lytic BKV infection on host cells at the molecular level are not well understood. Currently, there is no specific antiviral treatment for BKV-associated disease, and a better understanding of the complete life cycle of the virus is necessary. Here, we report the interplay between BKV and one of the regulatory structures in the host cell nucleus, promyelocytic leukemia nuclear bodies (PML-NBs). Our results show that BKV infection reorganizes PML-NBs as a strategy to inactivate the negative functions of PML-NBs.

scholarly journals Rhesus Macaque Rhadinovirus Encodes a Viral Interferon Regulatory Factor To Disrupt Promyelocytic Leukemia Nuclear Bodies and Antagonize Type I Interferon Signaling

2019 ◽  
Vol 93 (6) ◽  
Author(s):  
Laura K. Springgay ◽  
Kristin Fitzpatrick ◽  
Byung Park ◽  
Ryan D. Estep ◽  
Scott W. Wong
Keyword(s):  
Immune Response ◽  
Rhesus Macaque ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Type I ◽  
Type I Ifn ◽  
Regulatory Factors ◽  
Successful Infection ◽  
Promyelocytic Leukemia Nuclear Bodies

ABSTRACTInterferon (IFN) production and the subsequent induction of IFN-stimulated genes (ISGs) are highly effective innate strategies utilized by cells to protect against invading pathogens, including viruses. Critical components involved in this innate process are promyelocytic leukemia nuclear bodies (PML-NBs), which are subnuclear structures required for the development of a robust IFN response. As such, PML-NBs serve as an important hurdle for viruses to overcome to successfully establish an infection. Both Kaposi’s sarcoma-associated herpesvirus (KSHV) and the closely related rhesus macaque rhadinovirus (RRV) are unique for encoding viral homologs of IFN regulatory factors (termed vIRFs) that can manipulate the host immune response by multiple mechanisms. All four KSHV vIRFs inhibit the induction of IFN, while vIRF1 and vIRF2 can inhibit ISG induction downstream of the IFN receptor. Less is known about the RRV vIRFs. RRV vIRF R6 can inhibit the induction of IFN by IRF3; however, it is not known whether any RRV vIRFs inhibit ISG induction following IFN receptor signaling. In our present study, we demonstrate that the RRV vIRF R12 aids viral replication in the presence of the type I IFN response. This is achieved in part through the disruption of PML-NBs and the inhibition of robust ISG transcription.IMPORTANCEKSHV and RRV encode a unique set of homologs of cellular IFN regulatory factors, termed vIRFs, which are hypothesized to help these viruses evade the innate immune response and establish infections in their respective hosts. Our work elucidates the role of one RRV vIRF, R12, and demonstrates that RRV can dampen the type I IFN response downstream of IFN signaling, which would be important for establishing a successful infectionin vivo.

scholarly journals Swine Promyelocytic Leukemia Isoform II Inhibits Pseudorabies Virus Infection by Suppressing Viral Gene Transcription in Promyelocytic Leukemia Nuclear Bodies

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Cuilian Yu ◽  
Aotian Xu ◽  
Yue Lang ◽  
Chao Qin ◽  
Mengdong Wang ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Transcriptional Repression ◽  
Pseudorabies Virus ◽  
Promyelocytic Leukemia ◽  
Natural Host ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Viral Gene Transcription ◽  
C Terminus ◽  
Promyelocytic Leukemia Nuclear Bodies

ABSTRACT Promyelocytic leukemia nuclear bodies (PML-NBs) possess an important intrinsic antiviral activity against alphaherpesvirus infection. PML is the structural backbone of NBs, comprising different isoforms. However, the contribution of each isoform to alphaherpesvirus restriction is not well understood. Here, we report the role of PML-NBs and swine PML (sPML) isoforms in pseudorabies virus (PRV) infection in its natural host swine cells. We found that sPML-NBs exhibit an anti-PRV activity in the context of increasing the expression level of endogenous sPML. Of four sPML isoforms cloned and examined, only isoforms sPML-II and -IIa, not sPML-I and -IVa, expressed in a sPML knockout cells inhibit PRV infection. Both the unique 7b region of sPML-II and the sumoylation-dependent normal formation of PML-NBs are required. 7b possesses a transcriptional repression activity and suppresses viral gene transcription during PRV infection with the cysteine residues 589 and 599 being critically involved. We conclude that sPML-NBs inhibit PRV infection partly by repressing viral gene transcription through the 7b region of sPML-II. IMPORTANCE PML-NBs are nuclear sites that mediate the antiviral restriction of alphaherpesvirus gene expression and replication. However, the contribution of each PML isoform to this activity of PML-NBs is not well characterized. Using PRV and its natural host swine cells as a system, we have discovered that the unique C terminus of sPML isoform II is required for PML-NBs to inhibit PRV infection by directly engaging in repression of viral gene transcription. Our study not only confirms in swine cells that PML-NBs have an antiviral function but also presents a mechanism to suggest that PML-NBs inhibit viral infection in an isoform specific manner.

Heterodimer formation of the myeloid zinc finger 1 SCAN domain and association with promyelocytic leukemia nuclear bodies

2008 ◽  
Vol 32 (10) ◽  
pp. 1582-1592 ◽  
Author(s):  
LeAnne Noll ◽  
Francis C. Peterson ◽  
Paulette L. Hayes ◽  
Brian F. Volkman ◽  
Tara Sander
Keyword(s):  
Zinc Finger ◽  
Promyelocytic Leukemia ◽  
Nuclear Bodies ◽  
Promyelocytic Leukemia Nuclear Bodies ◽  
Myeloid Zinc Finger ◽  
Scan Domain
Sign in / Sign up

Export Citation Format

Share Document