Potential Role for Luman, the Cellular Homologue of Herpes Simplex Virus VP16 (α Gene
            <i>trans</i>
            -Inducing Factor), in Herpesvirus Latency

Lu, Rui; Misra, Vikram

doi:10.1128/jvi.74.2.934-943.2000

Cited by 81 publications

(97 citation statements)

References 54 publications

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“…8B, this species must be equally abundant. Proteins such as LZIP and ZF, which are present at very low levels in tissue culture cells (14,15), do not satisfy this criterion. We favor a second model shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells

Wysocka

Reilly

Herr

2001

Molecular and Cellular Biology

179

203

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Human HCF-1 is a large, highly conserved, and abundant nuclear protein that plays an important but unknown role in cell proliferation. It also plays a role in activation of herpes simplex virus immediate-early gene transcription by the viral regulatory protein VP16. A single proline-to-serine substitution in the HCF-1 VP16 interaction domain causes a temperature-induced arrest of cell proliferation in hamster tsBN67 cells and prevents transcriptional activation by VP16. We show here that HCF-1 is naturally bound to chromatin in uninfected cells through its VP16 interaction domain. HCF-1 is chromatin bound in tsBN67 cells at permissive temperature but dissociates from chromatin before tsBN67 cells stop proliferating at the nonpermissive temperature, suggesting that loss of HCF-1 chromatin association is the primary cause of the temperatureinduced tsBN67 cell proliferation arrest. We propose that the role of HCF-1 in cell proliferation is to regulate gene transcription by associating with a multiplicity of DNA-bound transcription factors through its VP16 interaction domain.

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Section: Discussionmentioning

confidence: 99%

Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells

Wysocka

Reilly

Herr

2001

Molecular and Cellular Biology

179

203

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“…Monoclonal antibodies against VP16 (LP1) as well as rabbit antisera against PML and HCF were obtained from Peter O'Hare, Marie Curie Institute, UK. The procedure for immunoblotting and immunofluorescence using the antibodies has been described previously (18,20). For co-immunoprecipitation experiments described in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Antibodies, Immunoblots, Immunofluorescence, and Immunoprecipitation-Antisera against Luman and Zhangfei were raised in rabbits or mice using recombinant GST fusion proteins purified from Escherichia coli (12,18). Monoclonal antibodies against VP16 (LP1) as well as rabbit antisera against PML and HCF were obtained from Peter O'Hare, Marie Curie Institute, UK.…”

Section: Methodsmentioning

confidence: 99%

“…Luman is a basic leucine-zipper (B-Zip) transcription factor that, in vitro, can bind cAMP and unfolded protein response elements (CRE and UPRE). Both proteins appear to be selectively expressed in neurons (18). 2 When Luman is ectopically synthesized in cultured cells, it can enhance the expression of reporter genes linked to promoters that contain CREs and UPREs in an HCFdependent manner (10,19).…”

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confidence: 99%

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Zhangfei Is a Potent and Specific Inhibitor of the Host Cell Factor-binding Transcription Factor Luman

Misra¹,

Rapin²,

Akhova³

et al. 2005

Journal of Biological Chemistry

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Host cell factor (HCF) was initially discovered as a cellular co-factor required for the activation of herpes simplex virus immediate early gene expression by the virion associated transactivator VP16. HCF also participates in a variety of cellular processes, although the mechanism of its action is not known. VP16 binds to HCF through a 4-amino acid motif (EHAY), which closely resembles the HCF binding domain of two cellular basic leucine-zipper proteins, Luman and Zhangfei. Luman is a powerful transcription factor that, in transient expression assays, activates promoters containing cAMP or unfolded protein response elements (UPRE). In contrast, Zhangfei neither binds consensus recognition elements for basic leucinezipper proteins nor does it activate promoters containing them. Here we show that Zhangfei suppresses the ability of Luman to activate transcription. HCF appeared to be required for efficient suppression. A mutant of Zhangfei, which was unable to bind HCF, was impaired in its ability to suppress Luman. Zhangfei did not suppress ATF6, a transcription factor closely related to Luman but that does not bind HCF, unless the HCF binding motif of Luman was grafted onto it. Zhangfei inhibited the HCF-dependent activation of a UPRE-containing promoter by a Gal4-Luman fusion protein but was unable to inhibit the HCF-independent activation by Gal4-Luman of a promoter that contained Gal4 binding motifs. Binding of HCF by Zhangfei was required for the co-localization of Luman and Zhangfei to nuclear domains, suggesting that HCF might target the proteins to a common location.

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“…It possesses a potent N-terminal acidic activation domain and a basic-leucine zipper motif (bZIP) (15,(23)(24)(25)(26). The primary structure of Luman appears to be strongly conserved, and Luman homologues in mice (LZIP [8]), cattle (our unpublished results), and fruit flies (dCREB-A/BBF-2 [1, 37]) have been identified.…”

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confidence: 99%

Luman, the Cellular Counterpart of Herpes Simplex Virus VP16, Is Processed by Regulated Intramembrane Proteolysis

Raggo

Rapin

Stirling

et al. 2002

Molecular and Cellular Biology

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125

135

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Luman is a human basic leucine zipper transcription factor that, like the herpes simplex virus transcription factor VP16, requires the host cell factor, HCF, for activity. Although both HCF and Luman have been implicated in cell growth, their biological roles have not been clearly defined. Luman conforms to a type II membrane-associated glycoprotein with its carboxyl terminus embedded in cellular membranes and its amino terminus, which contains all its identified functional domains, in the cytoplasm. Here we show that Luman is processed by regulated intramembrane proteolysis (RIP). The site 1 protease (S1P), a Golgi apparatusresident enzyme responsible for catalyzing the first step in the RIP pathway of the sterol regulatory element binding proteins (SREBPs) and ATF6, may also be involved in the processing of Luman. Thus, processing of Luman was highly stimulated by brefeldin A, a compound that causes the reflux of Golgi apparatus enzymes to the endoplasmic reticulum (ER). In addition, coexpression of Luman with S1P containing a KDEL ER retrieval signal resulted in virtually quantitative cleavage of Luman in the absence of any treatment. Finally, Luman contains a sequence, RQLR, immediately downstream from the transmembrane domain which bears similarity to the consensus S1P cleavage site identified by others. Substitution of arginine residues within this motif abolished S1P cleavage, providing robust evidence that S1P is involved in Luman processing. We observed that following S1P cleavage, the majority of the cleaved Luman was retained in cytoplasmic membranes, indicating that an additional step or enzymes yet to be identified are involved in complete cleavage and release to yield the product which ultimately enters the nuclei of cells.Luman (also known as LZIP and CREB3) is a basic leucine zipper transcription factor of the CREB/ATF gene family. It possesses a potent N-terminal acidic activation domain and a basic-leucine zipper motif (bZIP) (15,(23)(24)(25)(26). The primary structure of Luman appears to be strongly conserved, and Luman homologues in mice (LZIP [8]), cattle (our unpublished results), and fruit flies (dCREB-A/BBF-2 [1, 37]) have been identified. We and others (15, 24) originally identified Luman when screening for cellular ligands of the human host cell factor (HCF, also known as C1 factor), a protein required by the herpes simplex virus (HSV) transactivator VP16. Luman interacts with HCF through the tetrapeptide DHTY (15,24,25), which is homologous to the EHAY HCF binding sequence of VP16. This motif, as (D/E)HXY, is conserved in the VP16 homologues of other alphaherpesviruses as well as in the homologues of Luman in mice, cattle, and fruit flies. Luman can bind and activate genes containing cyclic AMP response elements (CREs), although its natural target has not been identified. Similarly, although Luman has been implicated in the regulation of cell growth (18), its biological role in this process has not been clearly defined. Luman mRNA is present in a wide range of adult and fetal tissues (...

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Potential Role for Luman, the Cellular Homologue of Herpes Simplex Virus VP16 (α Gene trans -Inducing Factor), in Herpesvirus Latency

Cited by 81 publications

References 54 publications

Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells

Loss of HCF-1–Chromatin Association Precedes Temperature-Induced Growth Arrest of tsBN67 Cells

Zhangfei Is a Potent and Specific Inhibitor of the Host Cell Factor-binding Transcription Factor Luman

Luman, the Cellular Counterpart of Herpes Simplex Virus VP16, Is Processed by Regulated Intramembrane Proteolysis

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