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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish
Pages (from-to)462-467
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume417
Issue number1
DOIs
Publication statusPublished - Jan 6 2012
Externally publishedYes

Fingerprint

Disintegrins
Amyloid Precursor Protein Secretases
Cell Adhesion Molecules
Metalloproteases
Tumors
Neoplasms
Proteolysis
Membranes
Spermatogenesis
Protease Inhibitors
Mast Cells
Synapses
Small Interfering RNA
Cell Survival
Glycoproteins
Tumor Necrosis Factor-alpha
Cells

Keywords

  • γ-Secretase
  • ADAM10
  • CADM1
  • RIP
  • Shedding
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

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; Futai, Eugene; Suo, Satoshi; Takaoka, Yutaka; Murakami, Yoshinori; Ito, Akihiko; Ishiura, Shoichi.

In: Biochemical and Biophysical Research Communications, Vol. 417, No. 1, 06.01.2012, p. 462-467.

Research output: Contribution to journalArticle

Nagara, Yusuke ; Hagiyama, Man ; Hatano, Naoya ; Futai, Eugene ; Suo, Satoshi ; Takaoka, Yutaka ; Murakami, Yoshinori ; Ito, Akihiko ; Ishiura, Shoichi. / Tumor suppressor cell adhesion molecule 1 (CADM1) is cleaved by a disintegrin and metalloprotease 10 (ADAM10) and subsequently cleaved by γ-secretase complex. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 417, No. 1. pp. 462-467.
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