Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex

Yusuke Nagara; Man Hagiyama; Naoya Hatano; Eugene Futai; Satoshi Suo; Yutaka Takaoka; Yoshinori Murakami; Akihiko Ito; Shoichi Ishiura

doi:10.1016/j.bbrc.2011.11.140

Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex

Yusuke Nagara, Man Hagiyama, Naoya Hatano, Eugene Futai, Satoshi Suo, Yutaka Takaoka, Yoshinori Murakami, Akihiko Ito^*, Shoichi Ishiura

^*Corresponding author for this work

Data Science Center for Medicine and Hospital Management

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

34 Scopus citations

Abstract

Cell adhesion molecule 1 (CADM1) is a type I transmembrane glycoprotein expressed in various tissues. CADM1 is a cell adhesion molecule with many functions, including roles in tumor suppression, apoptosis, mast cell survival, synapse formation, and spermatogenesis. CADM1 undergoes membrane-proximal cleavage called shedding, but the sheddase and mechanisms of CADM1 proteolysis have not been reported. We determined the cleavage site involved in CADM1 shedding by LC/MS/MS and showed that CADM1 shedding occurred in the membrane fraction and was inhibited by tumor necrosis factor-α protease inhibitor-1 (TAPI-1). An siRNA experiment revealed that ADAM10 mediates endogenous CADM1 shedding. In addition, the membrane-bound fragment generated by shedding was further cleaved by γ-secretase and generated CADM1-intracellular domain (ICD) in a mechanism called regulated intramembrane proteolysis (RIP). These results clarify the detailed mechanism of membrane-proximal cleavage of CADM1, suggesting the possibility of RIP-mediated CADM1 signaling.

Original language	English
Pages (from-to)	462-467
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	417
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2011.11.140
State	Published - 2012/01/06

Keywords

ADAM10
CADM1
RIP
Shedding
Tumor suppressor gene
γ-Secretase

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2011.11.140

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Nagara, Y., Hagiyama, M., Hatano, N., Futai, E., Suo, S., Takaoka, Y., Murakami, Y., Ito, A., & Ishiura, S. (2012). Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex. Biochemical and Biophysical Research Communications, 417(1), 462-467. https://doi.org/10.1016/j.bbrc.2011.11.140

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title = "Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex",

abstract = "Cell adhesion molecule 1 (CADM1) is a type I transmembrane glycoprotein expressed in various tissues. CADM1 is a cell adhesion molecule with many functions, including roles in tumor suppression, apoptosis, mast cell survival, synapse formation, and spermatogenesis. CADM1 undergoes membrane-proximal cleavage called shedding, but the sheddase and mechanisms of CADM1 proteolysis have not been reported. We determined the cleavage site involved in CADM1 shedding by LC/MS/MS and showed that CADM1 shedding occurred in the membrane fraction and was inhibited by tumor necrosis factor-α protease inhibitor-1 (TAPI-1). An siRNA experiment revealed that ADAM10 mediates endogenous CADM1 shedding. In addition, the membrane-bound fragment generated by shedding was further cleaved by γ-secretase and generated CADM1-intracellular domain (ICD) in a mechanism called regulated intramembrane proteolysis (RIP). These results clarify the detailed mechanism of membrane-proximal cleavage of CADM1, suggesting the possibility of RIP-mediated CADM1 signaling.",

keywords = "ADAM10, CADM1, RIP, Shedding, Tumor suppressor gene, γ-Secretase",

author = "Yusuke Nagara and Man Hagiyama and Naoya Hatano and Eugene Futai and Satoshi Suo and Yutaka Takaoka and Yoshinori Murakami and Akihiko Ito and Shoichi Ishiura",

note = "Funding Information: We thank Dr. Bart De Strooper (Vlaams Instituut voor Biotechnologie) for Presenilin 1/2 double knockout cells and Dr. Philip C. Wong (The Johns Hopkins University) for Nicastrin −/− cells. Y.N. is supported by a JSPS Research Fellowship for Young Scientists.",

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doi = "10.1016/j.bbrc.2011.11.140",

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Nagara, Y, Hagiyama, M, Hatano, N, Futai, E, Suo, S, Takaoka, Y, Murakami, Y, Ito, A & Ishiura, S 2012, 'Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex', Biochemical and Biophysical Research Communications, vol. 417, no. 1, pp. 462-467. https://doi.org/10.1016/j.bbrc.2011.11.140

Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex. / Nagara, Yusuke; Hagiyama, Man; Hatano, Naoya et al.
In: Biochemical and Biophysical Research Communications, Vol. 417, No. 1, 06.01.2012, p. 462-467.

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

TY - JOUR

T1 - Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex

AU - Nagara, Yusuke

AU - Hagiyama, Man

AU - Hatano, Naoya

AU - Futai, Eugene

AU - Suo, Satoshi

AU - Takaoka, Yutaka

AU - Murakami, Yoshinori

AU - Ito, Akihiko

AU - Ishiura, Shoichi

N1 - Funding Information: We thank Dr. Bart De Strooper (Vlaams Instituut voor Biotechnologie) for Presenilin 1/2 double knockout cells and Dr. Philip C. Wong (The Johns Hopkins University) for Nicastrin −/− cells. Y.N. is supported by a JSPS Research Fellowship for Young Scientists.

PY - 2012/1/6

Y1 - 2012/1/6

N2 - Cell adhesion molecule 1 (CADM1) is a type I transmembrane glycoprotein expressed in various tissues. CADM1 is a cell adhesion molecule with many functions, including roles in tumor suppression, apoptosis, mast cell survival, synapse formation, and spermatogenesis. CADM1 undergoes membrane-proximal cleavage called shedding, but the sheddase and mechanisms of CADM1 proteolysis have not been reported. We determined the cleavage site involved in CADM1 shedding by LC/MS/MS and showed that CADM1 shedding occurred in the membrane fraction and was inhibited by tumor necrosis factor-α protease inhibitor-1 (TAPI-1). An siRNA experiment revealed that ADAM10 mediates endogenous CADM1 shedding. In addition, the membrane-bound fragment generated by shedding was further cleaved by γ-secretase and generated CADM1-intracellular domain (ICD) in a mechanism called regulated intramembrane proteolysis (RIP). These results clarify the detailed mechanism of membrane-proximal cleavage of CADM1, suggesting the possibility of RIP-mediated CADM1 signaling.

AB - Cell adhesion molecule 1 (CADM1) is a type I transmembrane glycoprotein expressed in various tissues. CADM1 is a cell adhesion molecule with many functions, including roles in tumor suppression, apoptosis, mast cell survival, synapse formation, and spermatogenesis. CADM1 undergoes membrane-proximal cleavage called shedding, but the sheddase and mechanisms of CADM1 proteolysis have not been reported. We determined the cleavage site involved in CADM1 shedding by LC/MS/MS and showed that CADM1 shedding occurred in the membrane fraction and was inhibited by tumor necrosis factor-α protease inhibitor-1 (TAPI-1). An siRNA experiment revealed that ADAM10 mediates endogenous CADM1 shedding. In addition, the membrane-bound fragment generated by shedding was further cleaved by γ-secretase and generated CADM1-intracellular domain (ICD) in a mechanism called regulated intramembrane proteolysis (RIP). These results clarify the detailed mechanism of membrane-proximal cleavage of CADM1, suggesting the possibility of RIP-mediated CADM1 signaling.

KW - ADAM10

KW - CADM1

KW - RIP

KW - Shedding

KW - Tumor suppressor gene

KW - γ-Secretase

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U2 - 10.1016/j.bbrc.2011.11.140

DO - 10.1016/j.bbrc.2011.11.140

M3 - 学術論文

C2 - 22172944

AN - SCOPUS:84855781402

SN - 0006-291X

VL - 417

SP - 462

EP - 467

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex

Abstract

Keywords

ASJC Scopus subject areas

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