The Sac3 Homologue shd1 Is Involved in Mitotic Progression in Mammalian Cells

Khuda, Sefat E.; Yoshida, Mikoto; Xing, Yan; Shimasaki, Tatsuya; Takeya, Motohiro; Kuwahara, K.; Sakaguchi, Nobuo

doi:10.1074/jbc.m405347200

Cited by 14 publications

(20 citation statements)

References 26 publications

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“…The RNA-primase region and the RNA-binding activity might cooperate during the transcription at G 1 phase and introduce the alteration or the damage of the V H region sequences during rapid cell proliferation in GCs. More interestingly, altered expression of mouse SHD1 that has a homology to the central part of GANP (630 -950 aa) caused an apparent cell cycle abnormality involving with centrosome duplication and M phase transition (29), which was also in accordance with the information of the association of Saccharomyces Sac3 with Cdc31/centrin (30). Loss of SHD1 caused an impairment of centrosome duplication, deregulated nuclear division, with disappearance of Mad2 expression in the prometaphase.…”

Section: Discussionsupporting

confidence: 61%

Generation of High-Affinity Antibody against T Cell-Dependent Antigen in the Ganp Gene-Transgenic Mouse

Sakaguchi

Kimura²,

Matsushita³

et al. 2005

The Journal of Immunology

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Generation of high-affinity Ab is impaired in mice lacking germinal center-associated DNA primase (GANP) in B cells. In this study, we examined the effect of its overexpression in ganp transgenic C57BL/6 mice (GanpTg). GanpTg displayed normal phenotype in B cell development, serum Ig levels, and responses against T cell-independent Ag; however, it generated the Ab with much higher affinity against nitrophenyl-chicken gammaglobulin in comparison with C57BL/6. To further examine the affinity increase, we established hybridomas producing high-affinity mAbs and compared their affinities using BIAcore. C57BL/6 generated high-affinity anti-nitrophenyl mAbs (KD ∼ 2.50 × 10−7 M) of IgG1/λ1 and contained the VH186.2 region with W33L mutation. GanpTg generated much higher affinity (KD > 1.57 × 10−9 M) by usage of VH186.2 as well as noncanonical VH7183 regions. GanpTg also generated exceptionally high-affinity anti-HIV-1 (V3 peptide) mAbs (KD > 9.90 × 10−11 M) with neutralizing activity. These results demonstrated that GANP is involved in V region alteration generating high-affinity Ab.

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Section: Discussionsupporting

confidence: 61%

Generation of High-Affinity Antibody against T Cell-Dependent Antigen in the Ganp Gene-Transgenic Mouse

Sakaguchi

Kimura²,

Matsushita³

et al. 2005

The Journal of Immunology

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“…Three potential vertebrate homologues of Sac3 have been identified, GANP, MCM3AP, and Shd1 (1,58). B-cell germinal center-associated protein (GANP) and MCM3 associated protein (MCM3AP) are derived from the same gene by alternative splicing (1).…”

Section: Discussionmentioning

confidence: 99%

“…The third vertebrate relative of Sac3p, the Sac3 homology domain protein 1 (SHD1) is one-third the size of yeast Sac3p and lacks the yeast-centrin interaction domain (58). However, SHD1 localizes to centrosomes, and RNAi of SHD1 causes abnormalities in centrosome duplication and spindle formation (58).…”

Section: Discussionmentioning

confidence: 99%

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Centrin 2 Localizes to the Vertebrate Nuclear Pore and Plays a Role in mRNA and Protein Export

Resendes

Rasala

Forbes

2008

Molecular and Cellular Biology

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Centrins in vertebrates have traditionally been associated with microtubule-nucleating centers such as the centrosome. Unexpectedly, we found centrin 2 to associate biochemically with nucleoporins, including the Xenopus laevis Nup107-160 complex, a critical subunit of the vertebrate nuclear pore in interphase and of the kinetochores and spindle poles in mitosis. Immunofluorescence of Xenopus cells and in vitro reconstituted nuclei indeed revealed centrin 2 localized at the nuclear pores. Use of the mild detergent digitonin in immunofluorescence also allowed centrin 2 to be clearly visualized at the nuclear pores of human cells. Disruption of nuclear pores using RNA interference of the pore assembly protein ELYS/MEL-28 resulted in a specific decrease of centrin 2 at the nuclear rim of HeLa cells. Functionally, excess expression of either the Nor C-terminal calcium-binding domains of human centrin 2 caused a dominant-negative effect on both mRNA and protein export, leaving protein import intact. The mRNA effect mirrors that found for the Saccharomyes cerevisiae centrin Cdc31p at the yeast nuclear pore, a role until now thought to be unique to yeast. We conclude that in vertebrates, centrin 2 interacts with major subunits of the nuclear pore, exhibits nuclear pore localization, and plays a functional role in multiple nuclear export pathways.

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“…SHD1 was also reported to be involved in the mitotic progression of mammalian cells, as the suppression of SHD1 mRNA using siRNA resulted in abnormal centromere duplication and spindle assembly. 34 However, we did not observe any proliferative defects in SHD1 Ϫ/Ϫ T, B, and BM cells, and the SHD1-deficient mice were grossly normal with no growth retardation. The reason for these conflicting results is not clear at present.…”

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confidence: 51%

SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription

Nakajima

Tamura

Ito

et al. 2009

Blood

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STAT5 is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. During a search for STAT5-interacting proteins, we identified SHD1, a mammalian homologue of yeast gene Sac3, as a potential interacter. SHD1 was localized in the nucleus, and induced by cytokines that activate STAT5, such as erythropoietin, interleukin-2 (IL-2), or IL-3. SHD1 interacted specifically with STAT5A and STAT5B, and interestingly, it specifically repressed STAT5-dependent transcription in vitro without affecting the stability or phosphorylation of STAT5 protein. Gene disruption study revealed that IntroductionSignal transducer and activator of transcription (STAT) is one of the central mediators of cytokine signaling. 1 Of the 7 known members of mammalian STATs, 2 highly related STAT5 molecules, namely STAT5A and STAT5B, are considered to be of particular interest since they are activated by a wide array of cytokines including interleukin-2 (IL-2), IL-3, IL-5, IL-7, erythropoietin (Epo), and granulocyte macrophage-colony-stimulating factor (GM-CSF). 1 STAT5 is implicated in the self-renewal of hematopoietic stem cells 2 and is constitutively activated in a variety of leukemias, 3 indicating that STAT5 plays a critical role in normal and malignant hematopoiesis. 4 The activities of STATs are regulated by various protein modifications, such as tyrosine phosphorylation/dephosphorylation, serine phosphorylation, ubiquitination, and arginine methylation. 5 The phosphorylation and dephosphorylation of tyrosine residue is the most important posttranslational modification common to all STAT proteins, directly affecting dimerization, nuclear translocation and export, and DNA binding. 1,6,7 The phosphorylation of serine residue in the C-terminal activation domain is essential for the maximal transcriptional activity of STAT1. 8,9 Arginine methylation also affects the DNA-binding activity of STAT1. 10 Ubiquitination is particularly important for terminating the STAT activities by targeting the protein to the ubiquitin-proteasome degradation pathway. 11 These regulations are, in part, achieved by association of STATs with other regulatory molecules, which include SLIM and PIAS family of proteins. [12][13][14][15][16] In addition to protein modifications, STATs are also regulated at the level of transcription by associating with transcriptional coactivators and corepressors. STATs associate with CREB-binding protein (CBP)/p300, universal coactivators for many transcription factors, through the C-terminal activation domain. [17][18][19] We have previously shown that a nuclear receptor corepressor, SMRT, associated with STAT5 through its coiled-coil domain and repressed the STAT5-dependent transcription. 20 However, it remains unclear precisely how such transcriptional repression plays a role in the STAT5-dependent transcription in a physiological context.As is commonly seen with other signaling pathways, the Jak-STAT pathway also succumbs to the negative feedback regula...

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The Sac3 Homologue shd1 Is Involved in Mitotic Progression in Mammalian Cells

Cited by 14 publications

References 26 publications

Generation of High-Affinity Antibody against T Cell-Dependent Antigen in the Ganp Gene-Transgenic Mouse

Generation of High-Affinity Antibody against T Cell-Dependent Antigen in the Ganp Gene-Transgenic Mouse

Centrin 2 Localizes to the Vertebrate Nuclear Pore and Plays a Role in mRNA and Protein Export

SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription

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