Cdk2 activity is associated with depolarization of mitochondrial membrane potential during apoptosis

Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis

“…Thus, Cdk2, a key regulator of the cell cycle, has been suggested to play a role in apoptosis. In previous reports, we showed that the induction of cyclin A-Cdk2 activity, but not Cdc2 activity, is essential for the apoptotic progression of human hepatoma SK-HEP1 cells induced by ginsenoside Rh2 (Jin et al, 2000) and Panaxadiol (Jin et al, 2003). Other groups have shown that cyclin B-Cdc2 kinase activity is implicated in the paclitaxel-induced apoptosis of cells such as the human breast carcinoma cell line MCF-7 (Shen et al, 1998), the human cervical cell line HeLa cells (Donaldson et al, 1994), and the human hepatoma cell line HepG2 (Gagandeep et al, 1999).…”

“…Cdk1/cyclin B1 activity shields human cells against extrinsic death stimuli (Matthess et al, 2010). Cdk2 activation is mainly detected in apoptotic cells that exhibit G 1 /S phase arrest, as observed in ultraviolet irradiation-treated mesangial cells (Hiromura et al, 2002), etoposide-induced human leukemic cells (Choi et al, 2007;Bastin-Coyette et al, 2011), growth factor-deprived HUVEC cells (Levkau et al, 1998), G-Rh2-induced human hepatoma cells (Jin et al, 2000), panaxadiol-induced SK-HEP-1 cells (Jin et al, 2003). In previous reports, we showed that Cdk2 but not Cdc2 is selectively up-regulated and this upregulation is required for the induction of apoptosis in several cancer cell lines, including SK-HEP-1 cells and HeLa cells induced by treatment with ginsenoside-Rh2 (G-Rh2) (Jin et al, 2000) or panaxadiol (Jin et al, 2003).…”

Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer

“…The proapoptotic signaling of CDK2 is not clear yet. It has been reported that cytoplasmic CDK2 activity is induced in a caspasedependent way following activation of the Fas pathway (35) and leads to depolarization of the mitochondrial membrane potential (36) by cytoplasmic CDK2-mediated translocation of Bax to the mitochondria (36,37). Alternatively, functional interaction of CDK2 with FOXO1 after DNA damage can be an important mechanism to enhance, among others, Fas ligand expression (38).…”

Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis

“…For example, dysregulation of the components of the cell cycle machinery (leading to an aberrant cell cycle) has been reported to be one of the most potent stimuli for induction of apoptosis [23]. Unscheduled activation of Cdk molecules can induce apoptosis in several experimental settings, while inhibition of Cdk activity protects cells against apoptosis [24][25][26]. However, it is widely known that many chemotherapeutic drugs inhibit the activities of Cdks, leading to eventual cell death [27].…”