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Page 4 of 25 Kondapuram et al. J Cancer Metastasis Treat 2019;5:32 I http://dx.doi.org/10.20517/2394-4722.2018.105

Figure 2. Diagrammatic representation of various signals leading to the formation of autophagy initiation - ULK complex

Figure 3. Schematic representation of molecules involved in the (1) initiation; and (2) nucleation process leading to the autophagophore
formation during autophagy

During nucleation, vesicular sorting protein 34 and its enzymatic product phosphatidylinositol-3-phosphate,
an essential component play a vital role in recruiting other autophagy protein subunits such as WIPI-1,
DFCP1, ATG5 and LC3. The effectors WIPI-1, WIPI-2 and DFCP1, binds to PI3P via WD repeats and FYVE
domains, respectively [21,22] . In nucleation process, Vps34 associates with the phagophore membrane via p150
[Figure 3] that is anchored by myristic acid. Beclin-1 is the third important component for phospholipid
kinase activity. Activity of Beclin-1 is affected by many different binding partners. Beclin1 dissociates from
the anti-apoptotic factor Bcl2, which leads to the activation of Vps34. The association of beclin1 with Vps34
is stabilized by the other two components - UV radiation-associated resistance gene and beclin-1-associated
[23]
autophagy related key regulator .
Elongation step
In elongation step, the maturation of the autophagosome takes place with the help of two ubiquitin like
conjugation system [Figure 4]. In the early step of autophagosome maturation, Atg12 is activated by Atg7