CircuLex PCSK9-cIAP1 in vitro Binding Assay Kit

  • Target PCSK9-cIAP1
  • Code # CY-8152
  • Size 96 Assays
  • Price
    $595.00
Specifications

Background

PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) is a 692-residue extracellular protein expressed primarily in the kidneys, liver and intestines (1) representing the 9th member of the secretory subtilase family. Various genetic observations subsequently mapped PCSK9 as the third gene (along with LDLR and APOB) to cause autosomal dominant hypercholesterolemia (ADH). These studies suggested that gain of function mutations increase plasma levels of LDL-c (2–6), whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of PCSK9, lead to a reduction of plasma levels of LDL-c and an 88% decrease in the risk of coronary heart disease (CHD) (5). In mice, adenoviral overexpression of PCSK9 results in increased plasma LDL-c level in normal mice but not in LDLR-deficient mice (7). Deletion of PCSK9 causes an increase in level of LDLR protein but not mRNA (8). These findings lead to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing LDL-c from plasma. By shotgun proteomic analysis, Weiming Xu et al. identified cellular inhibitor of apoptosis protein-1 (cIAP1) as a binding partner of PCSK9 (9). They revealed that cIAP1 might regulate the activities of PCSK9 by two ways; promoting PCSK9 maturation from the proprotein form to the mature form and leading to ubiquitination of PCSK9 to lysosomal degradation. The following compelling evidences support this conclusion; Knockdown of c-IAP1 impairs PCSK9 processing and autocatalytic cleavage. In c-IAP1 null MEFs, there is a dramatic decrease in secreted mature PCSK9 protein, while in the wild-type MEF cells, proprotein form of the PCSK9 was properly processed and secreted into cell supernatants
  • Components:
    • Microplate
    • Recombinant His-tagged PCSK9 wild type
    • 150X HRP-conjugated anti-His-tag monoclonal antibody
    • Reaction Buffer
    • Conjugate Dilution Buffer
    • 10X Wash Buffer
    • Substrate Reagent
    • Stop Solution
  • Description:

    The CycLex Research Product CircuLex PCSK9-cIAP1 in vitro Binding Assay Kit is primarily designed to screening inhibitors of PCSK9-cIAP1 interaction in vitro.

  • Product Type:
    Kit
  • Short Description:

    CircuLex PCSK9-cIAP1 in vitro Binding Assay Kit.

  • Size:
    96 Assays
  • Storage Temperature:
    4°C
  • Target:
    PCSK9-cIAP1
References
  1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) Proc Natl Acad Sci USA 100:928–933.
  2. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, et al. (2003) Nat Genet 34:154–156.
  3. Leren TP (2004) Clin Genet 65:419–422.
  4. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, et al. (2005) Hum Mutat 26:497.
  5. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH (2006) N Engl J Med 354, 1264–1272.
  6. Berge KE, Ose L, Leren TP (2006) Arterioscler Thromb Vasc Biol 26:1094–1100.
  7. Maxwell KN, Breslow JL (2004) Proc Natl Acad Sci USA 101:7100–7105.
  8. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD (2005) Proc Natl Acad Sci USA 102:5374–5379.
  9. Xu W, Liu L, Hornby D. (2012) Molecules 2012, 17, 12086-12101