High impact information on Noxa1

• Mouse embryonic fibroblasts deficient in Noxa [Noxa(-/-) mouse embryonic fibroblasts (MEFs)] showed notable resistance to oncogene-dependent apoptosis in response to DNA damage, which was further increased by introducing an additional null zygosity for Bax [1].
• Noxa(-/-) mice showed resistance to X-ray irradiation-induced gastrointestinal death, accompanied with impaired apoptosis of the epithelial cells of small intestinal crypts, indicating the contribution of Noxa to the p53 response in vivo [1].
• To assess the in vivo relevance of these findings, we subjected mice lacking Puma, Noxa, or Bim to whole-body gamma-radiation or the glucocorticoid dexamethasone and compared lymphocyte survival with that in wild-type and BCL2-transgenic mice [2].
• p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation [3].
• The co-expression of Brn-3a and p53 results in decreased endogenous Noxa protein in the neuronal cell line, ND7, suggesting a direct functional effect of this interaction [4].

Biological context of Noxa1

• An antisense plasmid of Noxa1 attenuated the endogenous Noxa1 protein expression in VSMC [5].
• This effect requires the p53 binding site, and electrophoretic mobility shift assay studies suggest that Brn-3a is associated with p53 when it is bound to its site in the Noxa promoter [4].
• BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death [6].
• Unlike Noxa, the upregulation of PUMA alone is sufficient to induce neuronal cell death [7].
• Furthermore, the BH3-only proteins Noxa and PUMA exhibit differential regulation by the two transactivation domains [7].

Anatomical context of Noxa1

• Immunohistochemistry revealed that Noxa1 is expressed in the smooth muscle layer but not in endothelium or the adventitia of the mouse carotid artery [5].
• Western blot analysis revealed that human endothelial cells and leukocytes but not VSMC from the aorta of the rat and the mouse express the classic NADPH oxidase activator p67phox [5].
• In Noxa-deficient mice, axotomy-induced motor neuron death was suppressed [8].

Other interactions of Noxa1

• Nox is playing with a full deck in vascular smooth muscle, a commentary on "Noxa1 is a central component of the smooth muscle NADPH oxidase in mice" [9].

Analytical, diagnostic and therapeutic context of Noxa1

• We studied the role of Noxa, one of the transcriptional targets of p53 that encodes a proapoptotic protein of the Bcl-2 family, by the gene-targeting approach [1].
• Furthermore, among the BH3-only protein members examined, Noxa exhibited the most marked upregulation after axotomy in the mouse [8].

References