Inhibition of ubiquitin ligase Siah-1A by disabled-1

Tae Ju Park, Hiroki Hamanaka, Toshio Ohshima, Noriko Watanabe, Katsuhiko Mikoshiba, Nobuyuki Nukina

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Disabled-1 (Dab1) is a cytosolic adaptor protein that plays critical roles in cortical development. However, a detailed mechanism of action has not yet been clearly defined. Through yeast two-hybrid screening, we observed that mouse Siah-1A, an E3 ubiquitin ligase containing a RING finger motif, interacts with Dab1. Co-immunoprecipitation experiments and in vitro binding experiments both indicated direct interaction between Siah and Dab1. Steady-state expression of Siah was enhanced by the presence of Dab1 or lactacystin, a representative proteasomal inhibitor. Auto-ubiquitination of Siah was inhibited by the presence of Dab1, suggesting inhibition of Siah activity and subsequent increase of Siah expression by Dab1. Both Dab1-induced increase of steady-state expression of Deleted in cololectal cancer (DCC), one of the well-known substrates of Siah, and its inhibition by SiahΔR suggest that Dab1 increases expression of DCC through inhibiting the activity of endogenous Siah. Our results suggest that Dab1 inhibits the activity of Siah.

Original languageEnglish
Pages (from-to)671-678
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume302
Issue number4
DOIs
Publication statusPublished - 2003 Mar 21
Externally publishedYes

Fingerprint

Ligases
Ubiquitin
RING Finger Domains
Ubiquitin-Protein Ligases
Ubiquitination
Immunoprecipitation
Yeast
Neoplasms
Screening
Yeasts
Experiments
Substrates
Proteins
lactacystin
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibition of ubiquitin ligase Siah-1A by disabled-1. / Park, Tae Ju; Hamanaka, Hiroki; Ohshima, Toshio; Watanabe, Noriko; Mikoshiba, Katsuhiko; Nukina, Nobuyuki.

In: Biochemical and Biophysical Research Communications, Vol. 302, No. 4, 21.03.2003, p. 671-678.

Research output: Contribution to journalArticle

Park, Tae Ju ; Hamanaka, Hiroki ; Ohshima, Toshio ; Watanabe, Noriko ; Mikoshiba, Katsuhiko ; Nukina, Nobuyuki. / Inhibition of ubiquitin ligase Siah-1A by disabled-1. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 302, No. 4. pp. 671-678.
@article{ff0e554ad6274c86812882b840429fec,
title = "Inhibition of ubiquitin ligase Siah-1A by disabled-1",
abstract = "Disabled-1 (Dab1) is a cytosolic adaptor protein that plays critical roles in cortical development. However, a detailed mechanism of action has not yet been clearly defined. Through yeast two-hybrid screening, we observed that mouse Siah-1A, an E3 ubiquitin ligase containing a RING finger motif, interacts with Dab1. Co-immunoprecipitation experiments and in vitro binding experiments both indicated direct interaction between Siah and Dab1. Steady-state expression of Siah was enhanced by the presence of Dab1 or lactacystin, a representative proteasomal inhibitor. Auto-ubiquitination of Siah was inhibited by the presence of Dab1, suggesting inhibition of Siah activity and subsequent increase of Siah expression by Dab1. Both Dab1-induced increase of steady-state expression of Deleted in cololectal cancer (DCC), one of the well-known substrates of Siah, and its inhibition by SiahΔR suggest that Dab1 increases expression of DCC through inhibiting the activity of endogenous Siah. Our results suggest that Dab1 inhibits the activity of Siah.",
author = "Park, {Tae Ju} and Hiroki Hamanaka and Toshio Ohshima and Noriko Watanabe and Katsuhiko Mikoshiba and Nobuyuki Nukina",
year = "2003",
month = "3",
day = "21",
doi = "10.1016/S0006-291X(03)00247-X",
language = "English",
volume = "302",
pages = "671--678",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Inhibition of ubiquitin ligase Siah-1A by disabled-1

AU - Park, Tae Ju

AU - Hamanaka, Hiroki

AU - Ohshima, Toshio

AU - Watanabe, Noriko

AU - Mikoshiba, Katsuhiko

AU - Nukina, Nobuyuki

PY - 2003/3/21

Y1 - 2003/3/21

N2 - Disabled-1 (Dab1) is a cytosolic adaptor protein that plays critical roles in cortical development. However, a detailed mechanism of action has not yet been clearly defined. Through yeast two-hybrid screening, we observed that mouse Siah-1A, an E3 ubiquitin ligase containing a RING finger motif, interacts with Dab1. Co-immunoprecipitation experiments and in vitro binding experiments both indicated direct interaction between Siah and Dab1. Steady-state expression of Siah was enhanced by the presence of Dab1 or lactacystin, a representative proteasomal inhibitor. Auto-ubiquitination of Siah was inhibited by the presence of Dab1, suggesting inhibition of Siah activity and subsequent increase of Siah expression by Dab1. Both Dab1-induced increase of steady-state expression of Deleted in cololectal cancer (DCC), one of the well-known substrates of Siah, and its inhibition by SiahΔR suggest that Dab1 increases expression of DCC through inhibiting the activity of endogenous Siah. Our results suggest that Dab1 inhibits the activity of Siah.

AB - Disabled-1 (Dab1) is a cytosolic adaptor protein that plays critical roles in cortical development. However, a detailed mechanism of action has not yet been clearly defined. Through yeast two-hybrid screening, we observed that mouse Siah-1A, an E3 ubiquitin ligase containing a RING finger motif, interacts with Dab1. Co-immunoprecipitation experiments and in vitro binding experiments both indicated direct interaction between Siah and Dab1. Steady-state expression of Siah was enhanced by the presence of Dab1 or lactacystin, a representative proteasomal inhibitor. Auto-ubiquitination of Siah was inhibited by the presence of Dab1, suggesting inhibition of Siah activity and subsequent increase of Siah expression by Dab1. Both Dab1-induced increase of steady-state expression of Deleted in cololectal cancer (DCC), one of the well-known substrates of Siah, and its inhibition by SiahΔR suggest that Dab1 increases expression of DCC through inhibiting the activity of endogenous Siah. Our results suggest that Dab1 inhibits the activity of Siah.

UR - http://www.scopus.com/inward/record.url?scp=0037459166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037459166&partnerID=8YFLogxK

U2 - 10.1016/S0006-291X(03)00247-X

DO - 10.1016/S0006-291X(03)00247-X

M3 - Article

C2 - 12646221

AN - SCOPUS:0037459166

VL - 302

SP - 671

EP - 678

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -