Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Iino, Takashi; Takeuchi, Kaoru; Nam, Sung Min; Siomi, Haruhiko; Sabe, Hisataka; Kobayashi, Nobuyuki; Hatanaka, Masakazu

doi:10.1099/0022-1317-67-7-1373

Cited by 27 publications

(9 citation statements)

References 31 publications

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“…This difference in the predicted and observed masses may be attributable to the high content of acidic and proline residues comprising the PRLBP (21%). Previous studies have reported this same discrepancy because of the retarded mobility of a variety of proteins based on proline and acidic residue content (23)(24)(25). To confirm the identity of the PRLBP with the PRLR ECD, the immunoprecipitated PRLBP was subjected to limited proteolysis and SDS-polyacrylamide gel electrophoresis analysis alongside similarly digested rhPRLR ECD (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Kline

Clevenger

2001

Journal of Biological Chemistry

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The actions of prolactin (PRL) are mediated by its receptor, a member of the superfamily of single transmembrane cytokine receptors. High affinity binding proteins for the closely related growth hormone have been found in the sera of several species including humans and are generated by alternative splicing or proteolysis of the growth hormone receptor extracellular domain (ECD). In contrast, no conclusive evidence has been presented that an analogous prolactin-binding protein (PRLBP) is expressed in human serum. Using both monoclonal and polyclonal antibodies generated against hPRL and the ECD of the human prolactin receptor, co-immunoprecipitation analyses of human serum identified a 32-kDa hPRLBP capable of binding both hPRL and human growth hormone. A measurable fraction of circulating PRL (36%) was associated with the hPRLBP. Despite well documented sex differences in serum hPRL levels, there were no significant differences in the levels of hPRLBP found in the sera of normal adult males and females (15.3 ؎ 1.3 ng/ml versus 13.4 ؎ 0.8 ng/ml, respectively (mean ؎ S.E.)). Immunoprecipitation studies also detected the PRLBP in human milk albeit at lower concentrations than found in sera. Deglycosylation did not alter its electrophoretic mobility, indicating an absence of carbohydrate moieties and suggesting that the hPRLBP spans most of the PRLR ECD, a result confirmed by limited proteolysis and mass spectrometry. The potential function of this serum chaperone was assessed in vitro by the addition of recombinant hPRLBP to the culture medium of the PRL-dependent Nb2 T-cell line. These studies revealed that the hPRLBP antagonizes PRL action, inhibiting PRL-driven growth in a dose-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Kline

Clevenger

2001

Journal of Biological Chemistry

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“…It has been reported that MT-2 cells contain one complete provirus and seven defective proviral sequences (27). A 3.4-kb RNA transcript of the defective proviruses expresses a myristylated truncated Gag protein that is composed of MA, a truncated CA, a short pX region, and two long terminal repeats (28). The 3.4-kb RNA transcript and the truncated Gag proteins have previously been found packaged into virus particles produced from MT-2 cells (20).…”

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confidence: 99%

Analysis of Human T-Cell Leukemia Virus Type 1 Particles by Using Cryo-Electron Tomography

Cao

Maldonado

Grigsby

et al. 2015

J Virol

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The particle structure of human T-cell leukemia virus type 1 (HTLV-1) is poorly characterized. Here, we have used cryo-electron tomography to analyze HTLV-1 particle morphology. Particles produced from MT-2 cells were polymorphic, roughly spherical, and varied in size. Capsid cores, when present, were typically poorly defined polyhedral structures with at least one curved region contacting the inner face of the viral membrane. Most of the particles observed lacked a defined capsid core, which likely impacts HTLV-1 particle infectivity.

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“…In this cell line, besides a complete provirus, seven defective proviruses were detected by Southern hybridization, and four of them were found to be identical with a large internal deletion resulting in the 5Ј portion of the gag gene being linked to a pX region (15,16). These proviruses contained an open reading frame (ORF) coding for a chimeric protein (p28) composed of Gag (MA [matrix] and truncated CA [capsid]) and a short pX fragment (12). RNA transcripts for MT-2 cell defective provirus are packaged in virions and can be translated into a p28 chimeric protein (25), and they establish new provirus in culture (1).…”

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confidence: 99%

Chimeric Matrix Proteins Encoded by Defective Proviruses with Large Internal Deletions in Human T-Cell Leukemia Virus Type 1-Infected Humans

Morozov

Lagaye

Taylor

et al. 2000

J Virol

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Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other diseases. The mechanisms of virus pathogenesis are still obscure. The occurrence of defective proviruses in HTLV-1-infected cell lines and the peripheral blood mononuclear cells (PBMC) of infected individuals is a frequent feature of virus infection. We detected defective proviruses with large internal deletions in PBMC from ATLL and HAM/TSP patients and in asymptomatic HTLV-1 carriers. Seventeen PCR-amplified defective proviruses were sequenced, and three types of deletions were found. Besides truncated MA and the 5 end of the genome, truncated CA, truncated SU, and more frequently truncated TM linked to the pX region were detected. Reverse transcription-PCR analysis of PBMC from ATLL patients and asymptomatic carriers also revealed RNA transcripts with large internal deletions. Analysis of two RT-PCR cDNA clones confirmed a Gag-TM-pX structure of the transcripts. Most defective proviruses contained numerous internal stop codons, but some were capable of coding for the truncated MA linked to a variable out-of-frame peptide. Cloned defective proviruses with long open reading frames were subjected to in vitro transcription-translation followed by radioimmunoprecipitation, which showed expression of chimeric proteins between 8 and 12 kDa. Possible roles of defective proviruses and chimeric proteins are discussed, although there is no firm association with pathogenesis.The human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus which causes two distinct pathologies: adult T-cell leukemia/lymphoma (ATLL) (10, 27) and chronic progressive myelopathy-tropical spastic paraparesis (TSP), also called HTLV-1-associated myelopathy (HAM) (5, 26). Recent studies have suggested that HTLV-1 is also associated with other human diseases (23).Previous comparative studies of different HTLV-1 isolates indicated the following: the protein patterns of the viruses from cells of individuals with ATL and HAM/TSP were identical (6), DNA blotting (11, 33) and sequence comparisons of proviruses from ATLL and HAM/TSP revealed nearly 97% homology (4, 21), and restriction endonuclease analysis did not reveal any selected integration sites for the proviruses in the DNA of infected individuals (33). Occasional cases of ATLL associated with TSP-HAM pathology have been reported (14,24), and infection of a patient with blood from a HAM/TSP donor resulted in HAM/TSP in the recipient (8). Thus, different diseases in association with one virus remains a paradox of HTLV-1. The mechanisms by which the virus induces different diseases and the cofactors, either virus associated or host related, that contribute to different forms of disease manifestations or progression remain to be determined.Defective proviruses have been observed in cells from ATLL patients and could be important elements in pathogenesis (9,17,32). We have therefore compared the presence of defecti...

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Structural Analysis of p28 Adult T-Cell Leukaemia-associated Antigen

Cited by 27 publications

References 31 publications

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Identification and Characterization of the Prolactin-binding Protein in Human Serum and Milk

Analysis of Human T-Cell Leukemia Virus Type 1 Particles by Using Cryo-Electron Tomography

Chimeric Matrix Proteins Encoded by Defective Proviruses with Large Internal Deletions in Human T-Cell Leukemia Virus Type 1-Infected Humans

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