GCIP, a Novel Human Grap2 and Cyclin D Interacting Protein, Regulates E2F-mediated Transcriptional Activity

Xia, Chunzhi; Bao, Zhenmin; Tabassam, Fazal H.; Ma, Wenbin; Qiu, Mengsheng; Hua, Shao-bing; Liu, Mingyao

doi:10.1074/jbc.m002598200

Cited by 49 publications

(86 citation statements)

References 40 publications

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“…This study presents results that demonstrate a physical interaction between P0 and a novel protein, GCIP, a human Grap2 and Cyclin D Interacting Protein (Xia et al, 2000), which is also recognized as a human homolog of MAID protein (HHM) (Terai et al, 2000) and a D-type cyclininteracting protein 1 (DIP1) (Yao et al, 2000). We further show here that increased expression of P0 in cells could execute its oncogenic activity by inhibiting GCIPmediated reduction of Rb phosphorylation and enhance the expression of cyclin D1.…”

Section: Introductionsupporting

confidence: 53%

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Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells

et al. 2007

Oncogene

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The ribosomal acidic P0 protein, an essential component of the eukaryotic ribosomal stalk, was found to interact with the helix-loop-helix protein human Grap2 and cyclin D interacting protein (GCIP)/D-type cyclin-interacting protein 1/human homolog of MAID protein. Using in vivo and in vitro binding assays, we show that P0 can interact with the N and C termini of GCIP via its N-terminal 39-114 amino-acid residues. Although the P0-GCIP complex was detected mainly in cytoplasmic fraction, polysome profile analysis indicated that the P0-GCIP complex did not coelute with either polysomes or 60S ribosomes, suggesting that GCIP associates with the free form of P0 in the cytoplasm. Transfection of GCIP into MCF-7 cells resulted in decreased levels of pRb phosphorylation. Cotransfection of P0 with GCIP, however, resulted in GCIP-mediated reduction of pRb phosphorylation level which was repressed by P0. Furthermore, overexpression of P0 in breast cancer and hepatocellular cancer cell lines promoted cell growth and colony formation compared to control transfectants. Overexpression of P0 also increased cyclin D1 expression and phosphorylation of pRb at Ser780. Interestingly, P0 mRNA was overexpressed in 12 of 20 pairs of breast cancer/ normal breast specimens (60%). Together, these data indicate that P0 overexpression may cause tumorigenesis in breast and liver tissues at least in part by inhibiting GCIP-mediated tumor suppression.

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Section: Introductionsupporting

confidence: 53%

“…The GCIP protein was found to be expressed in various cell types and in most human tissues with the highest level of expression in the heart, muscle, peripheral blood leukocytes and brain (Xia et al, 2000).…”

Section: Identification Of Gcip As a P0-binding Proteinmentioning

confidence: 99%

Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells

et al. 2007

Oncogene

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“…(c) E2F transactivity in pCI-HLE, pCI-hTERT-HLE and 20 mM 5'-d(TTAGGG)-3'-treated pCI-hTERT-HLE (pCI-hTERT-HLE+1). The E2F transactivity reporter plasmids pG5E1BCAT and E2CAT, and the control vector pRSV-b-Gal were described elsewhere (Wang et al, 1999;Xia et al, 2000;Xiang et al, 2000). Protein extracts were prepared by three freezing ± thawing cycles.…”

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confidence: 99%

Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway

et al. 2002

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Telomerase is a specialized reverse transcriptase that extends telomeres of eukaryotic chromosomes. The catalytic core of human telomerase is composed of an RNA template known as hTER (human telomerase RNA) and a protein subunit named hTERT (human telomerase reverse transcriptase). We have been studying other functions of the telomerase besides its major role in telomere maintenance. In our previous work, we have demonstrated that the hTERT can functionally interact with a rabbit TER to regulate expression of other genes and also attenuate the induced apoptosis. Here we report that overexpression of hTERT in a human lens epithelial cell line accelerates growth of the transfected lens epithelial cells. Associated with the acceleration of cell growth, expression of p53, p21 and GCIP (Grap2 cyclin-D interacting protein) is downregulated in the hTERTtransfected cells. With the downregulation of p21 and GCIP, the retinoblastoma protein (RB) is completely hyperphosphorylated in the hTERT-transfected cells. As expected, in the presence of RB hyperphosphorylation, the E2F transactivity is upregulated. Inhibition of telomerase activity abolishes the observed growth acceleration and also the related molecular changes. Furthermore, expression of hTERT in telomerasenegative human lens epithelial cells derived from primary cultures also accelerates growth of the transfected cells. Taken together, our results suggest that hTERT, when overexpressed in human lens epithelial cells, accelerates cell growth rate through regulation of RB/E2F pathway and possibly other genes.

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“…Therefore, these adaptor proteins regulate immune cell signaling and activation by selectively forming signaling complexes with di erent molecules (Clements et al, 1999;Rudd, 1999). Grap2 is a new member of the Grb2 family of adaptor proteins (Qiu et al, 1998;Law et al, 1999;Xia et al, 2000). Grap2 shares similar structural organization as Grb2 and Grap with the N-and C-terminal SH3 domains and a central SH2 domain.…”

Section: Discussionmentioning

confidence: 99%

“…Immunoprecipitation and immunoblot analysis were carried out as described previously (Xia et al, 2000). In brief, cells were lysed with a cell extraction bu er (1% NP-40, 20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM EDTA, 1 mM Na 3 VO 4 , 2 mM PMSF and 20 mg/ml aprotinin, 3 mg/ml leupeptin, and 3 mg/ml aprotinin), and immunoprecipitated with the indicated antibodies or GST-fusion proteins.…”

Section: Peptides Antibodies Immunoprecipitation and Immunoblot Anamentioning

confidence: 99%

Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes

Xia

Ling

et al. 2001

Oncogene

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Immune cell-speci®c adaptor proteins create various combinations of multiprotein complexes and integrate signals from cell surface receptors to the nucleus, modulating the speci®city and selectivity of intracellular signal transduction. Grap2 is a newly identi®ed adaptor protein speci®cally expressed in lymphoid tissues. This protein shares 40 ± 50% sequence homology in the SH3 and the SH2 domain with Grb2 and Grap. However, the Grap2 protein has a unique 120-amino acid glutamineand proline-rich domain between the SH2 and Cterminal SH3 domains. The expression of Grap2 is highly restricted to lymphoid organs and T lymphocytes. In order to understand the role of this speci®c adaptor protein in immune cell signaling and activation, we searched for the Grap2 interacting protein in T lymphocytes. We found that Grap2 interacted with the hematopoietic progenitor kinase 1 (HPK1) in vitro and in Jurkat T cells. The interaction was mediated by the carboxyl-terminal SH3 domain of Grap2 with the second proline-rich motif of HPK1. Coexpression of Grap2 with HPK1 not only increased the kinase activity of HPK1 in the cell, but also had an additive e ect on HPK1 mediated JNK activation. Furthermore, over expression of Grap2 and HPK1 induced signi®cant transcriptional activation of c-Jun in the JNK signaling pathway and IL-2 gene reporter activity in stimulated Jurkat T cells. Therefore, our data suggest that the hematopoietic speci®c proteins Grap2 and HPK1 form a signaling complex to mediate the c-Jun NH 2 -terminal kinase (JNK) signaling pathway in T cells. Oncogene (2001) 20, 1703 ± 1714.

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GCIP, a Novel Human Grap2 and Cyclin D Interacting Protein, Regulates E2F-mediated Transcriptional Activity

Cited by 49 publications

References 40 publications

Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells

Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells

Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway

Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes

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