Sheddasen

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Sheddases , also shedding enzymes mentioned are membrane - enzymes from the class of proteases .

Schematic representation of the ectodomain shedding with a sheddase.

function

The sheddases are membrane-bound proteases that can cut the ectodomains of transmembrane proteins in the extracellular area . The preamble of this process is ectodomain shedding ( Engl. To shed = "drop"). If transmembrane antigens are cut, one speaks of antigen shedding .

family members

Many members of the ADAM metalloproteases and the β-secretases BACE1 and BACE2 are counted among the sheddases . The sheddases ADAM10 and BACE1 are particularly interesting for new therapeutic approaches to the treatment of Alzheimer's disease . While the α-secretase ADAM10 cuts the amyloid precursor protein (APP) in the desired way, this is not the case with BACE1. Various BACE1 inhibitors and ADAM10 stimulators are under development.

In oncology , ADAM10 aims to do the opposite, i.e. to inhibit its function. ADAM10 also cuts off the HER2 / neu receptor from the cell membrane. The HER2 / neu receptor, in turn, is an important target in the therapy of breast cancer with trastuzumab . Also betacellulin , an epidermal growth factor , is cut of ADAM10. Other molecules that play an important role in the proliferation, differentiation , cell adhesion and cell migration of cancer cells , such as Notch , E-cadherin and CD44 , are also processed by this sheddase.

ADAM8 is a sheddase for CD23 and L-selectin and plays an important role in allergic inflammatory reactions .

Individual evidence

  1. ↑ G. Weskamp et al: ADAM10 is a principal sheddase of the low-affinity immunoglobulin E receptor CD23. In: Nat Immunol 7, 2006, pp. 1293-1298. PMID 17072319
  2. ^ SF Lichtenthaler and H. Steiner: Sheddases and intramembrane-cleaving proteases: RIPpers of the membrane. Symposium on regulated intramembrane proteolysis. In: EMBO Rep 8, 2007, pp. 537-541. PMID 17496832
  3. ↑ ML Moss et al: ADAM10 as a target for anti-cancer therapy. In: Curr Pharm Biotechnol 9, 2008, pp. 2-8. PMID 18289051
  4. ↑ M. Matsuno et al.: ADAM8 in allergy. In: Inflamm Allergy Drug Targets 7, 2008, pp. 108-112. PMID 18691140 (Review)

literature

  • NM Hooper and U. Lendeckel: The Adam Family of Proteases. Verlag Birkhäuser, 2005, ISBN 0-387-25149-9
  • DR Edwards et al: The ADAM metalloproteinases. In: Mol Aspects Med 29, 2008, pp. 258-289. PMID 18762209 (Review)
  • K. Reiss and P. Saftig: The "a disintegrin and metalloprotease" (ADAM) family of sheddases: physiological and cellular functions. In: Semin Cell Dev Biol 20, 2009, pp. 126-137. PMID 19049889