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Fig. 4 | Journal of Experimental & Clinical Cancer Research

Fig. 4

From: Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma

Fig. 4

Bcl-2 Regulation. Red arrows depict the interactions of downstream gene products when RKIP expression is high and black arrows depict the interactions of downstream gene products when RKIP expression is low. 1: Under normal conditions, high RKIP leads to low NF-κB expression, and thus Bcl-2 expression is low. In cancer cells, low RKIP expresses leads to high NF-κB and thus high Bcl-2 expression [61]; 2: Pten expression inhibits Bcl-2 [9]; 3: When Bcl-2 is expressed, it may alternatively bind BH3 [96, 97]; 4: Available Bcl-2 can form a bound complex with BH3 [96, 97]; 5: When Bcl-2 is bound to BH3, this leads to inactivation of Bcl-2, which has anti-apoptotic activity. Thus, if Bcl-2 is inactivated, apoptosis can occur [96, 97]; 6: Bcl-2 sequesters tBID (truncated BID) [96, 97]; 7: Bcl-2 can form a complex with tBID [96, 97]; 8: When RKIP expression is high normally, this leads to downstream activation of Pten, which inhibits AKT. When RKIP expression is low, this leads to low Pten levels, and thus AKT is expressed [13]; 9: AKT expression leads to BAD inactivation, whereas low AKT allows for available activated BAD [96, 97]; 10: When BAD is in its activated form, in can react with Bcl-2. Calcineurin B complex activates BAD, which replaces tBID, thus binding Bcl-2 [96, 97]; 11: When BAD binds Bcl-2, this leads to Bcl-2 activation [96, 97]; 12: The activation of Bcl-2 leads to anti-apoptotic activity. When Bcl-2 is not activated, apoptosis can occur [96, 97]

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