KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

Bentz, Gretchen L.; Bheda-Malge, Anjali; Wang, Sheng; Shackelford, Julia; Damania, Blossom; Pagano, Joseph S.

doi:10.1016/j.virol.2013.10.018

Cited by 14 publications

(11 citation statements)

References 60 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported that UCH-L1 expression is upregulated during EBV-mediated transformation of B-lymphocytes ( 52 ) and by expression of LMP1 in epithelial cells ( 50 ). However, whether LMP1 is directly associated with UCH-L1 was still unclear.…”

Section: Resultsmentioning

confidence: 99%

“…Expression of UCH-L1 in an adult organism is restricted to the central nervous and reproductive systems, but its de novo expression has been reported in numerous cancers such as lung cancer ( 45 , 46 ), colorectal cancer ( 47 ), bladder cancer ( 48 ), and breast cancer ( 49 ). Tumor viruses such as EBV, human papillomavirus (HPV), and Kaposi’s sarcoma-associated herpesvirus (KSHV) also induce UCH-L1 expression during cell transformation ( 50 – 54 ). A substantial amount of published data has demonstrated that UCH-L1 acts as a pro-oncogenic and prometastatic molecule in cell culture and in animal model systems ( 46 , 51 , 55 – 60 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes

Kobayashi

Aga

Kondo

et al. 2018

mSphere

View full text Add to dashboard Cite

Exosomes are small vesicles that cells secrete into the extracellular space, and there is increasing evidence that they have pivotal roles in cell-to-cell communication in malignancy. It is reported also that EBV-associated malignant cells, including those derived from nasopharyngeal carcinoma (NPC) and B-cell lymphoma, secrete exosomes. These EBV-related exosomes may contain viral products such as latent membrane protein 1 (LMP1) and may contribute to cancer progression. The aim of this study was to investigate the mechanism by which those viral products are loaded in exosomes. In this study, we show for the first time that ubiquitin C-terminal hydrolase-L1 (UCH-L1) and its C-terminal farnesylation, a posttranslational lipid modification, contribute to this mechanism. Our results also suggest that inhibition of UCH-L1 farnesylation is a potential therapeutic target against cancer metastasis and invasion.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes

Kobayashi

Aga

Kondo

et al. 2018

mSphere

View full text Add to dashboard Cite

show abstract

“… 116 In general, LMP1 activation leads to overexpression of antiapoptotic molecules, such as B-cell CLL/lymphoma 2 (Bcl-2), 117 myeloid cell leukemia 1 (Mcl-1) 118 and BCL-2-related protein A1 (Bcl2A1/Bfl-1), 116 , 119 and blocks p53-mediated apoptosis through the induction of anti-apoptotic protein A20, 120 unfolded protein response (UPR)-induced apoptosis in B cells 116 and ubiquitin C-terminal hydrolase L1 (UCH-L1) with oncogenic properties. 121 Complementary to its proliferative function, LMP1 inhibits proapoptotic factors such as Bax 122 and induces autocrine factors, such as chemokine (C–C motif) ligand 3 (CCL3) and chemokine (C–C motif) ligand 4 (CCL4), to promote cell proliferation. 123 LMP1 also enhances cancer cell motility by upregulating TNF α-induced protein 2 (TNFAIP2) through NF-κB activation.…”

Section: Epstein-barr Virusmentioning

confidence: 99%

Oncogenes and RNA splicing of human tumor viruses

Ajiro¹,

Zheng

2014

Emerging Microbes & Infections

View full text Add to dashboard Cite

Approximately 10.8% of human cancers are associated with infection by an oncogenic virus. These viruses include human papillomavirus (HPV), Epstein–Barr virus (EBV), Merkel cell polyomavirus (MCV), human T-cell leukemia virus 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis C virus (HCV) and hepatitis B virus (HBV). These oncogenic viruses, with the exception of HCV, require the host RNA splicing machinery in order to exercise their oncogenic activities, a strategy that allows the viruses to efficiently export and stabilize viral RNA and to produce spliced RNA isoforms from a bicistronic or polycistronic RNA transcript for efficient protein translation. Infection with a tumor virus affects the expression of host genes, including host RNA splicing factors, which play a key role in regulating viral RNA splicing of oncogene transcripts. A current prospective focus is to explore how alternative RNA splicing and the expression of viral oncogenes take place in a cell- or tissue-specific manner in virus-induced human carcinogenesis.

show abstract

“…Using previously described siRNA constructs and methods, Raji cells were transiently transfected to knockdown LMP1, with a two-base mutation siRNA used as a control 61 .…”

Section: Methodsmentioning

confidence: 99%

The Epstein-Barr Virus Oncoprotein, LMP1, Regulates the Function of SENP2, a SUMO-protease

Selby

Biel

Varn

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) activates numerous signal transduction pathways using its C-terminal activating regions. We reported that LMP1 increased global levels of sumoylated proteins, which aided the oncogenic nature of LMP1. Because increased protein sumoylation is detected in numerous cancers, we wanted to elucidate additional mechanisms by which LMP1 modulates the sumoylation machinery. Results indicated that SUMO-protease activity decreased in a LMP1-dependent manner, so we hypothesized that LMP1 inhibits SUMO-protease activity, resulting in reduced de-sumoylation of cellular proteins, which contributes to the detected accumulation of sumoylated proteins in EBV-positive lymphomas. Focusing on SENP2, findings revealed that LMP1 expression corresponded with increased sumoylation of SENP2 at K48 and K447 in a CTAR-dependent manner. Interestingly, independent of LMP1-induced sumoylation of SENP2, LMP1 also decreased SENP2 activity, decreased SENP2 turnover, and altered the localization of SENP2, which led us to investigate if LMP1 regulated the biology of SENP2 by a different post-translational modification, specifically ubiquitination. Data showed that expression of LMP1 inhibited the ubiquitination of SENP2, and inhibition of ubiquitination was sufficient to mimic LMP1-induced changes in SENP2 activity and trafficking. Together, these findings suggest that LMP1 modulates different post-translational modifications of SENP2 in order to modulate its biology and identify a third member of the sumoylation machinery that is manipulated by LMP1 during latent EBV infections, which can affect oncogenesis.

show abstract

KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

Cited by 14 publications

References 60 publications

C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes

C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes

Oncogenes and RNA splicing of human tumor viruses

The Epstein-Barr Virus Oncoprotein, LMP1, Regulates the Function of SENP2, a SUMO-protease

Contact Info

Product

Resources

About