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. 2015 Aug;11(3):229–237. doi: 10.2174/1573403X10666141106104606

Fig. (2).

Fig. (2)

Transcriptional, post-transcriptional and post-translational regulation of Beclin 1. Transcription factor including NF-κB, E2F, Stat3 as well as XBP1 isoform and signaling pathways such as AMPK-MEK/ERK-TSC-mTOR and JNK regulate beclin 1 gene transcription. miR- 376a, miR-376b, miR-21, miR-216b, miR-17-5p, miR-130a and miR-30a regulate beclin 1 gene expression at the post-transcriptional level. Human Beclin 1 protein is phosphorylated at S15 (ULK1), S90 (AMPK), S93 (AMPK), S108 (MST1), T119 (DAPK), Y229 (EGFR), Y233 (EGFR), S234 (Akt), S295 (Akt) and Y352 (EGFR) by the kinases indicated in the bracket. TRAF6 and Ambra1 ubiquitinate Beclin 1 protein at K117 and K437, respectively. Beclin 1 protein is cleavable by caspases at D124, D133, D146 and D149, generating an N-terminal and a C-terminal fragments. The C-terminal fragment resulting from cleavage at Asp-133 and Asp-149 has been demonstrated to promote apoptosis. Beclin 1 is also cleaved by calpain. S: Ser; T: Thr; Y: Tyr; D: Asp; K: Lys. Ⓜ: methylation.

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