Cdk5 regulates IP3R1-mediated Ca dynamics and Ca-mediated cell proliferation.

Loss of cyclin-dependent kinase 5 (Cdk5) in the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) increases ER-mitochondria tethering and ER Ca transfer to the mitochondria, subsequently increasing mitochondrial Ca concentration ([Ca]). This suggests a role for Cdk5 in regulating intracellular Ca dynamics, but how Cdk5 is involved in this process remains to be explored. Using ex vivo primary mouse embryonic fibroblasts (MEFs) isolated from Cdk5 mouse embryos, we show here that loss of Cdk5 causes an increase in cytosolic Caconcentration ([Ca]), which is not due to reduced internal Ca store capacity or increased Ca influx from the extracellular milieu.

mPTP opening caused by Cdk5 loss is due to increased mitochondrial Ca uptake.

We previously demonstrated that loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death by inducing mitochondrial permeability transition pore (mPTP) opening (Oncogene 37, 1788-1804). However, the molecular mechanism by which Cdk5 loss causes mPTP opening remains to be investigated. Using primary mouse embryonic fibroblasts (MEFs) isolated from Cdk5 mouse embryos, we show that absence of Cdk5 causes a significant increase in both mPTP opening and mitochondrial Ca level.

ROS-Mediated Cancer Cell Killing through Dietary Phytochemicals.

Reactive oxygen species (ROS) promote carcinogenesis by inducing genetic mutations, activating oncogenes, and raising oxidative stress, which all influence cell proliferation, survival, and apoptosis. Cancer cells display redox imbalance due to increased ROS level compared to normal cells. This unique feature in cancer cells may, therefore, be exploited for targeted therapy.

Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through dysregulation of the mitochondrial permeability transition pore.

Cdk5, which plays a role in the development and progression of many human cancers, localizes in the mitochondria, a key determinant of apoptotic cell death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss increases chemotherapy-induced apoptosis. However, the molecular mechanism by which Cdk5 loss promotes cell death remains unclear.

Targeting HSP90/Survivin using a cell permeable structure based peptido-mimetic shepherdin in retinoblastoma.

Background: Retinoblastoma (RB) is a childhood retinal malignancy. Effective therapeutic strategies are still being investigated in RB disease management. Here, the anti-cancer effect of shepherdin, a peptido-mimetic inhibiting heat shock protein (HSP90)-Survivin interaction has been analyzed.

RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.

T lymphoma invasion and metastasis protein (Tiam1) is up-regulated in variety of cancers and its expression level is related to metastatic potential of the type of cancer. Earlier, Tiam1 was shown to be overexpressed in retinoblastoma (RB) and we hypothesized that it was involved in invasiveness of RB. This was tested by silencing Tiam1 in RB cell lines (Y79 and Weri-Rb1) using siRNA pool, targeting different regions of Tiam1 mRNA.