Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation

Tuna Toptan, Lidia Fonseca, Hyun Jin Kwun, Yuan Chang, Patrick S. Moore

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ~50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1S. Higher-molecular-weight LANA1S isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1S isoforms initiate downstream within the central repeat 1 domain. LANA1S proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.

Original languageEnglish (US)
Pages (from-to)2744-2755
Number of pages12
JournalJournal of virology
Volume87
Issue number5
DOIs
StatePublished - Mar 1 2013

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Human herpesvirus 8
nuclear antigens
protein isoforms
Human Herpesvirus 8
translation (genetics)
Protein Isoforms
Oncogene Proteins
shoulders
Viral Gene Expression Regulation
Molecular Weight
molecular weight
Nuclear Localization Signals
nuclear localization signals
Proteins
proteins
latency-associated nuclear antigen
Polyacrylamide Gel Electrophoresis
plasmids
Plasmids
Maintenance

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

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title = "Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation",
abstract = "Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ~50{\%} of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1S. Higher-molecular-weight LANA1S isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1S isoforms initiate downstream within the central repeat 1 domain. LANA1S proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.",
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Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation. / Toptan, Tuna; Fonseca, Lidia; Kwun, Hyun Jin; Chang, Yuan; Moore, Patrick S.

In: Journal of virology, Vol. 87, No. 5, 01.03.2013, p. 2744-2755.

Research output: Contribution to journalArticle

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AU - Moore, Patrick S.

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