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Noxa: at the tip of the balance between life and death - PubMed

Review

Noxa: at the tip of the balance between life and death

C Ploner et al. Oncogene. 2008 Dec.

Abstract

Among all Bcl2 homology domain 3 (BH3)-only proteins known to date, APR/PMAIP1/Noxa, albeit showing weak proapoptotic potential on its own, appears to be crucial in fine-tuning cell death decisions by targeting the prosurvival molecule Mcl1 for proteasomal degradation. This event appears critical for cell death induction along the mitochondrial Bcl2-regulated apoptosis pathway in response to factor deprivation or DNA damage, presumably by sensitizing the cell toward the action of additional BH3-only protein family members. This review aims to summarize the function of Noxa in normal physiology, stress-induced cell death and tumorigenesis.

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Figures

Figure 1
Figure 1

(a) Sequence comparison of the human, mouse and rat Noxa protein. The mitochondrial targeting sequence (MTD) and the Bcl2 homology domain 3 (BH3) domains (A- and B motif) are shown in bold, respectively. (b) Sequence alignment of BH3 domains from ancestral Egl-1, related CED-13 and Noxa from different species. (c) Noxa gene structure, transcription factor binding sites and reported mRNA transcripts. Untranslated regions and intronic sequences are shown in white, coding sequence in black.

Figure 2
Figure 2

Multiple signals can induce Noxa expression. Noxa transcription and protein expression can be activated by diverse apoptotic or mitogenic signals in a p53-dependent as well as -independent manner. Noxa exerts its proapoptotic function mainly by neutralizing the prosurvival Bcl2 proteins Mcl1/A1, facilitating activation of Bax and/or Bak proteins.

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