Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Epididymal proteins represent the factors necessary for maturation of sperm and play a crucial role in sperm maturation. HE-4, an epididymal protein, is a member of whey acidic protein four-disulfide core (WFDC) family with no known function. A WFDC protein has a conserved WFDC domain of 50 amino acids with eight conserved cystine residue. HE-4 is a 124 amino acid long polypeptide with two WFDC domains. Here, we show that HE-4 is secreted in the human seminal fluid as a disulfide-bonded homo-trimer and is a cross-class protease inhibitor inhibits some of the serine, aspartyl and cysteine proteases tested using hemoglobin as a substrate. Using SPR we have also observed that HE-4 shows a significant binding with all these proteases. Disulfide linkages are essential for this activity. Moreover, HE-4 is N-glycosylated and highly stable on a wide range of pH and temperature. Taken together this suggests that HE-4 is a cross-class protease inhibitor which might confer protection against microbial virulence factors of proteolytic nature.

Related collections

Most cited references 51

Record: found
Abstract: found
Article: not found

Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis.

H Schägger, W.A. Cramer, G. Vonjagow (1994)

Blue native Electrophoresis is a "charge shift" method developed for isolation of native membrane protein complexes from biological membranes that also separates both acidic and basic water-soluble proteins at a fixed pH of 7.5. In combination with a second dimension sodium dodecylsulfate electrophoresis it provides an analytical method for the determination of molecular mass and oligomeric state of nondissociated complexes, of subunit composition, and of degree of purity and for the detection of subcomplexes. The method was applied to analysis of cytochrome bc/bf complexes. By combination of a novel colorless native polyacrylamide gel electrophoresis (CN-PAGE) with blue native BN-PAGE, a two-dimensional native technique was developed that is suitable for preparation of highly pure membrane protein complexes.

0 comments Cited 171 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comprehensive analysis of HE4 expression in normal and malignant human tissues.

Henry Frierson Jr., Mary T Galgano, Garret M. Hampton (2006)

The HE4 (WFDC2) gene encodes a WAP-type four disulphide core domain-containing protein with a presumptive role in natural immunity. Multiple studies have consistently identified upregulation of HE4 gene expression in carcinomas of the ovary; however, the expression in normal and malignant adult tissues has not been examined in detail. Here, we examined the expression of the HE4 gene and protein in a large series of normal and malignant adult tissues by oligonucleotide microarray and tissue microarray, respectively. HE4 gene expression was highest in normal human trachea and salivary gland, and to a lesser extent, lung, prostate, pituitary gland, thyroid, and kidney. In a series of 175 human adult tumors, gene expression was highest in ovarian serous carcinomas. However, adenocarcinomas of the lung, and occasional breast, transitional cell and pancreatic carcinomas had moderate or high levels of HE4 expression. Using tissue microarrays and full tissue sections of normal and 448 neoplastic tissues, HE4 immunoreactivity was found in normal glandular epithelium of the female genital tract and breast, the epididymis and vas deferens, respiratory epithelium, distal renal tubules, colonic mucosa, and salivary glands, consistent with HE4 gene expression. In addition to consistent positivity in ovarian carcinoma, some pulmonary, endometrial, and breast adenocarcinomas, mesotheliomas, and less often, gastrointestinal, renal and transitional cell carcinomas were also positive. Knowledge of the expression patterns of HE4 in our survey is useful for application in histopathologic diagnosis, and should be taken into consideration in future studies that examine the role of HE4 as a serological tumor biomarker or as a target for gene-based therapy.

0 comments Cited 113 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Gene expression patterns in ovarian carcinomas.

Sandra Caldeira, Hanne Skomedal, Giuseppe Ciaravino … (2003)

We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.

0 comments Cited 92 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

William R. Abrams: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2012

Publication date (Electronic): 5 November 2012

Volume: 7

Issue: 11

Electronic Location Identifier: e47672

Affiliations

[1 ]Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India

[2 ]Department of Lab Medicine, All India Institute of Medical Sciences, New Delhi, India

New York University, United States of America

Author notes

* E-mail: savita11@ 123456gmail.com

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: NC MS SY. Performed the experiments: NC AKT. Analyzed the data: NC MS SD SY. Contributed reagents/materials/analysis tools: SD SS. Wrote the paper: NC AKT MS SY.

[¤]

Current address: Centre for Bioanalytical Sciences, Dublin City University, Glasnevin, Dublin-9, Ireland

Article

Publisher ID: PONE-D-12-10538

DOI: 10.1371/journal.pone.0047672

PMC ID: 3489902

PubMed ID: 23139753

SO-VID: 8d1da527-423c-4226-a2e3-d4f13430d020

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 13 April 2012

Date accepted : 18 September 2012

Page count

Pages: 12

Funding

This work was supported by financial grants from the Department of Science and Technology (DST), Government of India. The authors thank the Council of Scientific and Industrial Research (CSIR), New Delhi for the fellowship granted to NC. The authors also thank Department of Science and Technology (DST), Government of India, for providing fellowship to AK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor

Read this article at

Abstract

Related collections

PLOS Climate

Most cited references 51

Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis.

Comprehensive analysis of HE4 expression in normal and malignant human tissues.

Gene expression patterns in ovarian carcinomas.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 436

Cited by 19

Most referenced authors 748