Detection of a secreted metalloprotease within the nuclei of liver cells

Ryan C. Hunt; S. Geetha; Courtni E. Allen; Klilah Hershko; Robert Fathke; Philip L. Kong; Elizabeth Plum; Evi Budo Struble; Kenji Soejima; Scott Friedman; Susan Garfield; S. Balaji; Chava Kimchi-Sarfaty

doi:10.1039/c0mb00303d

Detection of a secreted metalloprotease within the nuclei of liver cells

Ryan C. Hunt, S. Geetha, Courtni E. Allen, Klilah Hershko, Robert Fathke, Philip L. Kong, Elizabeth Plum, Evi Budo Struble, Kenji Soejima, Scott Friedman, Susan Garfield, S. Balaji, Chava Kimchi-Sarfaty

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus.

Original language	English
Pages (from-to)	2012-2018
Number of pages	7
Journal	Molecular BioSystems
Volume	7
Issue number	6
DOIs	https://doi.org/10.1039/c0mb00303d
State	Published - 1 Jun 2011

Access to Document

10.1039/c0mb00303d

Cite this

@article{262a4443f2984aafaa6fa3ba225c1a1f,

title = "Detection of a secreted metalloprotease within the nuclei of liver cells",

abstract = "ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus.",

author = "Hunt, {Ryan C.} and S. Geetha and Allen, {Courtni E.} and Klilah Hershko and Robert Fathke and Kong, {Philip L.} and Elizabeth Plum and Struble, {Evi Budo} and Kenji Soejima and Scott Friedman and Susan Garfield and S. Balaji and Chava Kimchi-Sarfaty",

year = "2011",

month = jun,

day = "1",

doi = "10.1039/c0mb00303d",

language = "English",

volume = "7",

pages = "2012--2018",

journal = "Molecular BioSystems",

issn = "1742-206X",

publisher = "Royal Society of Chemistry",

number = "6",

}

TY - JOUR

T1 - Detection of a secreted metalloprotease within the nuclei of liver cells

AU - Hunt, Ryan C.

AU - Geetha, S.

AU - Allen, Courtni E.

AU - Hershko, Klilah

AU - Fathke, Robert

AU - Kong, Philip L.

AU - Plum, Elizabeth

AU - Struble, Evi Budo

AU - Soejima, Kenji

AU - Friedman, Scott

AU - Garfield, Susan

AU - Balaji, S.

AU - Kimchi-Sarfaty, Chava

PY - 2011/6/1

Y1 - 2011/6/1

N2 - ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus.

AB - ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus.

UR - http://www.scopus.com/inward/record.url?scp=79956116963&partnerID=8YFLogxK

U2 - 10.1039/c0mb00303d

DO - 10.1039/c0mb00303d

M3 - Article

C2 - 21479334

AN - SCOPUS:79956116963

SN - 1742-206X

VL - 7

SP - 2012

EP - 2018

JO - Molecular BioSystems

JF - Molecular BioSystems

IS - 6

ER -

Detection of a secreted metalloprotease within the nuclei of liver cells

Abstract

Access to Document

Fingerprint

Cite this