SUMO and KSHV Replication
Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence sug...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2014-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/6/4/1905 |
| _version_ | 1797713974588866560 |
|---|---|
| author | Pei-Ching Chang Hsing-Jien Kung |
| author_facet | Pei-Ching Chang Hsing-Jien Kung |
| author_sort | Pei-Ching Chang |
| collection | DOAJ |
| description | Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis. |
| first_indexed | 2024-03-12T07:45:11Z |
| format | Article |
| id | doaj.art-b05154e11c664f1ca610604b7c60ecf3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:45:11Z |
| publishDate | 2014-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b05154e11c664f1ca610604b7c60ecf32023-09-02T21:04:49ZengMDPI AGCancers2072-66942014-09-01641905192410.3390/cancers6041905cancers6041905SUMO and KSHV ReplicationPei-Ching Chang0Hsing-Jien Kung1Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, TaiwanInstitute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, TaiwanSmall Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.http://www.mdpi.com/2072-6694/6/4/1905KSHVSUMOepigeneticPML-NBinterferon |
| spellingShingle | Pei-Ching Chang Hsing-Jien Kung SUMO and KSHV Replication Cancers KSHV SUMO epigenetic PML-NB interferon |
| title | SUMO and KSHV Replication |
| title_full | SUMO and KSHV Replication |
| title_fullStr | SUMO and KSHV Replication |
| title_full_unstemmed | SUMO and KSHV Replication |
| title_short | SUMO and KSHV Replication |
| title_sort | sumo and kshv replication |
| topic | KSHV SUMO epigenetic PML-NB interferon |
| url | http://www.mdpi.com/2072-6694/6/4/1905 |
| work_keys_str_mv | AT peichingchang sumoandkshvreplication AT hsingjienkung sumoandkshvreplication |