Understanding Noxa Regulation of Apoptosis

Wed, 02/05/2014 - 10:45

Noxa is a pro-apoptotic gene belonging to the Bcl2 protein family that is unique in that it contains only BH3 domain. The BH3-only subclass of proteins, including proteins like PUMA and Bim in addition to Noxa, regulate the remaining Bcl-2 family members. Due to the key roles these proteins play in this critical pathway, BH3-only proteins have great promise as therapeutic targets for cancers such as leukemias, as well as autoimmune diseases, as discussed in extensive reviews by Zhang, et al. and Cottier, et al. (1,2).

Immunohistochemistry-Paraffin: Noxa Antibody Immunohistochemistry-Paraffin: Noxa Antibody

The Noxa antibody helped researchers investigate the role of specific Bcl-xL chemical modifications in conferring selective apoptotic susceptibility to tumor cells while sparing normal cell phenotypes (3). Yakovlev’s group used the Noxa antibody to create a compelling model of an intrinsic p53-dependent apoptotic cascade involving the induction of BOK and Noxa in a BAX-independent mechanism (4). Immunofluorescent assays with the Noxa antibody allowed Wong, et al. to generate high-throughput, yet data-rich, quantitative analyses and clear visualization of Bcl-2 and BH3-only protein interactions and complexes in live cells (5). Their Noxa antibody methodology addressed a lack of tools to perform such detailed assessments, and resulted in the generation of a large body of suitable data to characterize the activity of putative therapeutic molecules targeting these crucial apoptotic pathways. Experiments with the Noxa antibody in myeloid cell leukemias suggests a link between the myeloid cell leukemia-1 protein (MCL1) with impaired autophagy and cardiotoxicity, in addition to its previously known role as a tumor-upregulated anti-apoptotic BCL-2 protein (6).

  1. PMID: 24352336
  2. PMID: 23175245
  3. PMID: 12372300
  4. PMID: 15102863
  5. PMID: 22460384
  6. PMID: 23788623

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