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Aryl Hydrocarbon Signaling: AIP, AhR, ARNT, BMAL1 and more...

Wed, 12/11/2013 - 08:39


AH receptor-interacting protein (AIP) is a 37 kD immunophilin-like factor found in a variety of tissues with expression levels ranging from high (spleen, thymus, pituitary heart, placenta and skeletal muscle) to low (liver, kidney and lung). It mediates aryl hydrocarbon receptor (AhR) signaling either through ligand receptivity and/or modulating nuclear targeting and has been shown to bind to both the AhR itself as well as the AhR nuclear translocator (ARNT). Historically it was originally identified as a negative regulator for the hepatitis B virus X-associated protein. Mouse knockout studies using the AIP antibody allowed researchers to determine that the association of AIP with survivin mediates mitochondrial import of survivin and protects tumor cells from apoptosis (1).

Western Blot: AIP/ARA9 Antibody Western Blot: AIP/ARA9 Antibody

For studies on AhR’s role in wound healing, Kasai’s group employed the AIP antibody in a human colon carcinoma cell system to demonstrate that adherens junction destruction triggers a CYP1A1/Slug response in a beta catenin dependent fashion through direct association with AhR (2). It is well-established that germline AIP mutations predispose individuals to pituitary adenomas (PA) especially in familial-isolated PA and this is an area of intense study. AIP antibody was used in real-time RT-PCR studies coupled with immunohistochemistry (IHC) to monitor both AIP and AhR in a large study of PA samples. IHC was found to have low sensitivity in screening for AIP mutations, possibly due to variable involvement of AhR signaling between different PA phenotypes (3). More encouraging IHC studies with AIP antibodies found that ARNT downregulation correlates with AIP mutation positive PAs (4). Trivellin’s lab found upregulation of the small noncoding microRNA miR-107 in both GH-secreting and nonfunctioning PA samples (5). AIP antibody allowed them to identify and confirm that AIP is a miR-107 target gene and that the two work together to stimulate tumorigenesis.

  1. PMID: 21454573
  2. PMID: 23174221
  3. PMID: 19556287
  4. PMID: 19850893
  5. PMID: 22811466

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