Cellular Localization and Expression of Template-Activating Factor I in Different Cell Types

Nagata, Kyosuke; Saito, Shoko; Okuwaki, Mitsuru; Kawase, Hiroyuki; Furuya, Akiko; Kusano, Akira; Hanai, Nobuo; Okuda, Asuko; Kikuchi, Akihiko

doi:10.1006/excr.1997.3930

Cited by 112 publications

(131 citation statements)

References 17 publications

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“…Newman,personal communication). In mammals, SET is found predominantly in the cell nuclei (35), whereas yeast Nap1 has been found to localize to the cytoplasm (31), and Drosophila Nap1 has been found to change its subcellular localization from nucleus to cytoplasm in a cell cycle-dependent manner (33,36). The finding of SPR-2::GFP in the nucleus is consistent with our assignment of SPR-2 to the SET subfamily based on sequence analysis.…”

Section: Spr-2 Is a Member Of The Set͞nap Protein Familysupporting

confidence: 81%

spr-2 , a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans , is a member of the SET protein subfamily

Wen

Levitan²,

Li³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Presenilin plays critical roles in the genesis of Alzheimer's disease and in LIN-12͞Notch signaling during development. Here, we describe a screen for genes that influence presenilin level or activity in Caenorhabditis elegans. We identified four spr (suppressor of presenilin) genes by reverting the egg-laying defective phenotype caused by a null allele of the sel-12 presenilin gene. We analyzed the spr-2 gene in some detail. We show that loss of spr-2 activity suppresses the egg-laying defective phenotype of different sel-12 alleles and requires activity of the hop-1 presenilin gene, suggesting that suppression is accomplished by elevating presenilin activity rather than by bypassing the need for presenilin activity. We also show that SPR-2 is a nuclear protein and is a member of a protein subfamily that includes human SET, which has been identified in numerous different biochemical assays and at translocation breakpoints associated with a subtype of acute myeloid leukemia.A key factor in the development of Alzheimer's disease is the deposition of plaques formed from A␤ peptides. These peptides are released when the single-pass transmembrane protein ␤-amyloid precursor protein (␤-APP) is cleaved at the ␤ site in the extracellular domain and at a ␥ site in the transmembrane domain. Studies of familial Alzheimer's disease led to the identification of the presenilin 1 and presenilin 2 genes (reviewed in ref. 1). Presenilin is required for ␥-secretase cleavage of ␤-APP (2, 3), and the two presenilins seem to be functionally interchangeable (4-6). Studies with putative aspartyl proteaseactive site inhibitors indicate that presenilin may itself be the long elusive ␥-secretase (7,8).Presenilin is being intensively pursued as a key therapeutic target for the amelioration or prevention of Alzheimer's disease. The identification of factors that influence presenilin activity, synthesis, and stability will be important for maximizing the efficacy of drugs that are targeted against ␥-secretase and perhaps for identifying new therapeutic targets. Genetic analysis of presenilin in Caenorhabditis elegans offers one approach to identifying such factors.In C. elegans, there are two presenilins, sel-12 and hop-1, that can be studied by virtue of their involvement in LIN-12͞Notch signal transduction (9, 10). LIN-12͞Notch proteins are transmembrane proteins that act as receptors for intercellular signals that specify cell fates. Ligand binding to LIN-12͞Notch receptors leads to proteolytic cleavage within the transmembrane domain, which releases the intracellular domain so that it may translocate to the nucleus and activate transcription of target genes (see 11, 12). The transmembrane-cleavage event is analogous to the ␥-secretase-processing event that generates A␤ from ␤-amyloid precursor protein, and presenilin is essential also for the proteolytic cleavage that releases the intracellular domain of LIN12͞Notch proteins (11,12). Indeed, in C. elegans, concomitant depletion of both sel-12 and hop-1 activity causes the phenotypes as...

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Section: Spr-2 Is a Member Of The Set͞nap Protein Familysupporting

confidence: 81%

spr-2 , a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans , is a member of the SET protein subfamily

Wen

Levitan²,

Li³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…Antibodies used in this study were as follows: anti-CAF-Ip150 (clone SS1) and anti-Asf1b antibodies gifts from Alain Verreault (University of Montreal, Canada); anti-NAP-1, anti-Spt16 and anti-histone H1 (clone AE4) antibodies from SantaCruz Biotech; anti-NASP antibody from ProteinTech Group; anti-histone H3 and anti-histone H1X antibodies from Abcam; anti-b-actin, anti-FLAG-tag and anti-His-tag antibodies from Sigma; anti-GFP antibody from Nacalai tesque; anti-HA-tag antibody (clone 3F10) from Roche; anti-TAF-Ib antibody (monoclonal antibody KM1720; Kirin-Kyowa Hakko) (Nagata et al, 1998); anti-TAF-I polyclonal antibody, which was generated in rabbits using recombinant TAFIbDC3 as an antigen. For indirect immunofluorescence analyses, antibodies conjugated to Alexa Fluor 488 and Alexa Fluor 568 were from Invitrogen.…”

Section: Antibodies and Indirect Immunofluorescence Analysesmentioning

confidence: 99%

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Kato

Okuwaki

Nagata

2011

Journal of Cell Science

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SummaryLinker histone H1 is a fundamental chromosomal protein involved in the maintenance of higher-ordered chromatin organization. The exchange dynamics of histone H1 correlates well with chromatin plasticity. A variety of core histone chaperones involved in core histone dynamics has been identified, but the identity of the linker histone chaperone in the somatic cell nucleus has been a longstanding unanswered question. Here we show that Template Activating Factor-I (TAF-I, also known as protein SET) is involved in histone H1 dynamics as a linker histone chaperone. Among previously identified core histone chaperones and linker histone chaperone candidates, only TAF-I was found to be associated specifically with histone H1 in mammalian somatic cell nuclei. TAF-I showed linker histone chaperone activity in vitro. Fluorescence recovery after photobleaching analyses revealed that TAF-I is involved in the regulation of histone H1 dynamics in the nucleus. Therefore, we propose that TAF-I is a key molecule that regulates linker histonemediated chromatin assembly and disassembly.

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“…To construct plasmids for expression in mammalian cells, DNA fragments of interest were first cloned into pBluescript and then recloned in-frame into the pCHA vector 23,24 providing an HAepitope tag under the control of the CMV enhancer and chicken ␤-actin promoter. CAN and Nup88 cDNAs were synthesized by the RT-PCR method using HeLa cell mRNA with primers 5Ј-TAGCTAGCATACGCGTGTAGGCGCGATGGGAGACGAGAT-GGATGC-3Ј for 5Ј end of CAN, 5Ј-TAGCTAGCATACGCGT-TATCAGCTTCGCCAGCCAGCCACCAA-3Ј for 3Ј end of CAN, 5Ј-CATGCCATGGCATATGGCGGCCGCCGAGGGA-3Ј for 5Ј end of Nup88, and 5Ј-CATGCCATGGATCGATTCAGAAGTT-TACATGATTGCGG-3Ј for 3Ј end of Nup88, and cloned into EcoRI-and SmaI-digested pBluescript and NcoI-and ClaI-digested pET14b, respectively.…”

Section: Preparation Of Plasmids and Protein Expressionmentioning

confidence: 99%

“…The proteins present in immunoprecipitates were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electrophoretically transferred to a PVDF membrane. The membrane was subjected to western blotting using anti-HA (Roche, 3F10), anti-TAF-I␤ (KM1721), 23 anti-CAN, and anti-hCRM1 antibodies.…”

Section: Immunoprecipitation and Immunoblottingmentioning

confidence: 99%

Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export

Saito

Miyaji-Yamaguchi

Nagata

2004

Intl Journal of Cancer

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The SET-CAN fusion gene is the product of a chromosomal rearrangement found on 9q34 associated with an acute undifferentiated leukemia. SET-CAN encodes an almost complete SET protein fused to the C-terminal two-thirds of CAN. SET is also known as TAF-I␤, a histone chaperone and intracellular inhibitor of protein phosphatase 2A, whereas CAN is identical to Nup214, a nucleoporin protein. To obtain insight into the leukemogenic function of SET/TAF-I␤-CAN/ Nup214, we have examined its subcellular localization. Immunofluorescence analyses showed that SET/TAF-I␤ and CAN/Nup214 are found in the nucleus and the nuclear envelope, respectively, whereas the majority of SET/TAF-I␤-CAN/Nup214 is localized in the nucleus. SET/TAF-I␤-CAN/ Nup214 interacted with hCRM1, one of the nuclear export factors, and caused aberrant intracellular localization of hCRM1. In cells expressing SET/TAF-I␤-CAN/Nup214, a protein containing a nuclear export signal accumulated in the nucleus. The export of this protein was partially restored by overexpression of hCRM1. These results suggest that aberrantly localized molecules associated with SET/TAF-I␤-CAN/ Nup214 may be involved in oncogenesis.

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Cellular Localization and Expression of Template-Activating Factor I in Different Cell Types

Cited by 112 publications

References 17 publications

spr-2 , a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans , is a member of the SET protein subfamily

spr-2 , a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans , is a member of the SET protein subfamily

Role of Template Activating Factor-I as a chaperone in linker histone dynamics

Aberrant intracellular localization of SET‐CAN fusion protein, associated with a leukemia, disorganizes nuclear export

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