Characterization of human N8 protein

Chen, Shin-Lin; Zhang, Xian-Kui; Halverson, David; Byeon, Mee Kyeong; Schweinfest, Clifford W.; Ferris, Douglas K.; Bhat, Narayan K.

doi:10.1038/sj.onc.1201437

Cited by 22 publications

(14 citation statements)

References 5 publications

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“…A potential cytoskeletal role for CRHSP-28 in epithelial cell function was described previously based on the finding that its expression is induced dramatically after activation of an epithelial gene program in mesenchymal cells by the adenoviral E1a protein (23). The E1a protein induces the expression of a number of epithelial specific cytoskeletal regulatory proteins including desmoplakin, desmogelin, desmocolin, E-cadherin, and the cytokeritins K8/K18 (40).…”

Section: Discussionmentioning

confidence: 99%

“…Also known as D52 (21), N8 (22,23), R10 (24), and CSPP-28 (25), this protein has been identified based on its overexpression in transformed epithelial cells (21,22,24) and Ca 2ϩ -sensitive phosphorylation in gastric mucosa (25). Moreover, Byrne et al (26) demonstrated that CRHSP-28 belongs to a novel tumor protein D52 family (TPD52) comprised of at least three homologous genes that may undergo alternative splicing to create different protein products (27).…”

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confidence: 99%

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CRHSP-28 Regulates Ca2+-stimulated Secretion in Permeabilized Acinar Cells

Thomas

Taft

Kaspar

et al. 2001

Journal of Biological Chemistry

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CRHSP-28 is a Ca2؉ -regulated heat-stable phosphoprotein, abundant in the apical cytoplasm of epithelial cells that are specialized in exocrine protein secretion. To define a functional role for the protein in pancreatic secretion, recombinant CRHSP-28 (rCRHSP-28) was introduced into streptolysin-O-permeabilized acinar cells, and amylase secretion in response to elevated Ca 2؉ was determined. Secretion was enhanced markedly by rCRHSP-28 over a time course that closely corresponded with the loss of the native protein from the intracellular compartment. No effects of rCRHSP-28 were detected until ϳ50% of the native protein was lost from the cytosol. Secretion was enhanced by rCRHSP-28 over a physiological range of Ca 2؉ concentrations with 2-3-fold increases in amylase release occurring in response to low micromolar levels of free Ca 2؉ . Further, rCRHSP-28 augmented secretion in a concentration-dependent manner with minimal and maximal effects occurring at 1 and 25 g/ml, respectively. Covalent cross-linking experiments demonstrated that native CRHSP-28 was present in a 60-kDa complex in cytosolic fractions and in a high molecular mass complex in particulate fractions, consistent with the slow leak rate of the protein from streptolysin-O-permeabilized cells. Probing acinar lysates with rCRHSP-28 in a gel-overlay assay identified two CRHSP-28-binding proteins of 35 (pp35) and 70 kDa (pp70). Interestingly, preparation of lysates in the presence of 1 mM Ca 2؉ resulted in a marked redistribution of both proteins from a cytosolic to a Triton X-100-insoluble fraction, suggesting a Ca 2؉ -sensitive interaction of these proteins with the acinar cell cytoskeleton. In agreement with our previous study immunohistochemically localizing CRHSP-28 around secretory granules in acinar cells, gel-overlay analysis revealed pp70 copurified with acinar cell secretory granule membranes. These findings demonstrate an important cell physiological function for CRHSP-28 in the Ca 2؉ -regulated secretory pathway of acinar cells.Exocrine cells specializing in protein secretion release a variety of factors necessary for normal function of the digestive, urogenital, respiratory, and ocular systems. Activation of these epithelia by neural and humoral agents stimulates the exocytosis of secretory granules at the apical plasma membrane in a process that is largely controlled by cellular Ca 2ϩ . In pancreatic acinar cells, Ca 2ϩ release is initiated in the apical pole and then propagates through the cell periphery to the basal cytoplasm. The cyclic reuptake and release of Ca 2ϩ from intracellular stores create an oscillatory mode of signaling with spatial and temporal characteristics that are unique to the specific type and concentration of physiologic stimulus (for review, see Refs. 1-3). Although the high concentrations of Ca 2ϩ generated in the apical cytoplasm are necessary for secretory granule trafficking and exocytosis to occur, a comprehensive understanding of the molecular events elicited by this ion is lacking.The secretory pathway in ac...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

CRHSP-28 Regulates Ca2+-stimulated Secretion in Permeabilized Acinar Cells

Thomas

Taft

Kaspar

et al. 2001

Journal of Biological Chemistry

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“…38,39 Enzymes such as lactate dehydrogenase, 40 protein disul®de isomerase (thyroid hormone binding protein) 41 ± 43 and catechol Omethyltransferase 44 ± 46 have also been shown to be overexpressed in a variety of tumor tissues. The gene that encodes N8L (D52 homolog, a leucine zipper protein) 47,48 is located at chromosome 8q21, a region that is frequently ampli®ed in breast cancer cells. 49 Pini et al 53 performed phage antibody selection on a recombinant protein, ED-B of ®bronectin, eluted from a 2D gel.…”

Section: Discussionmentioning

confidence: 99%

Towards proteome-wide production of monoclonal antibody by phage display

Liu

Huang

Sihlbom

et al. 2002

Journal of Molecular Biology

105

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“…PrLZ is expressed specifically in human prostate in an androgen-responsive manner, mainly in the epithelial compartment. The COOH-terminal region of PrLZ is identical to tumor protein D52 (TPD52), which has been isolated due to its abnormally elevated expression in breast cancer (3) and lung cancer (4). In the NH 2 -terminal region, however, PrLZ extends with a unique sequence of 46 amino acid residues.…”

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PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Wang

Mabjeesh

et al. 2007

Clinical Cancer Research

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Purpose: We previously reported the isolation and characterization of PrLZ, a novel prostatespecific and androgen-responsive gene of the tumor protein D52 family at chromosome 8q21.1. PrLZ is the only known gene in this locus with prostate specificity. Expression level of PrLZ was elevated specifically in cancer cells, suggesting its association with malignancy. Experimental Design:To define its biological function in the morphogenesis, development, and functional maturation of the prostate gland and to gain further insight into its role in prostate cancer, we examined PrLZ expression in prostate specimens during early embryonic development and in adult tissue. Results: PrLZ first appears in the nuclei of the prostate epithelia at 16 weeks of gestation before its distribution in the cytoplasm at later ages. Its expression peaks at 24 years of age, declines at 31years of age, and maintains a minimal level in later age. On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis. Overexpression of PrLZ in prostate cancer cells accelerates their growth in vitro and tumor formation in vivo. Conclusion: This work identifies PrLZ as a marker for prostate cancer progression and metastasis, andits pattern of expression is suggestive of a proto-oncogene.

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Characterization of human N8 protein

Cited by 22 publications

References 5 publications

CRHSP-28 Regulates Ca2+-stimulated Secretion in Permeabilized Acinar Cells

CRHSP-28 Regulates Ca2+-stimulated Secretion in Permeabilized Acinar Cells

Towards proteome-wide production of monoclonal antibody by phage display

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

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