Fig. 8: Model of PON2 post-transcriptional regulation. | Cell Death & Disease

Fig. 8: Model of PON2 post-transcriptional regulation.

From: WTAP and BIRC3 are involved in the posttranscriptional mechanisms that impact on the expression and activity of the human lactonase PON2

Fig. 8

In the model are reported data of protein–protein interactions for WTAP and BIRC3, and their relationship with PON2 as deduced from this paper and literature. Whereas BIRC3 can interact with WTAP via TAB1, modulation by ubiquitination it is also possible. WTAP binds a conserved sequence of some mRNAs of the cluster controlling its own splicing (in the nucleus) and stability (in the cytosol)66 and those of PON2 and BIRC3 (their mRNA are kept low). BIRC3 in turn controls PON2 splicing (based on our data), likely acting on WTAP, and on translation by acting on SREBP2 (based on chipseq data)78. It is worthwhile to notice that BIRC3 inhibits CASP3 activity by mono-Ub66,76,77 and that PON2 and BIRC3 both increase following WTAP silencing (this work). CASP3 hyper-activates SREBP2, which in turn activates the expression of PON2 (and maybe of BIRC3 based again on chipseq data)78. Therefore, the increase of BIRC3 has a negative feedback effect on itself and on PON2 expression, splicing, and activity. 3OC12HSL stimulates PON2 ubiquitination but BIRC3, however, does not ubiquitinate PON2 in our system.

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