The c-Jun NH(2)-terminal kinase (JNK) is activated when cells are exposed to environmental stress, including UV radiation. Gene disruption studies demonstrate that JNK is essential for UV-stimulated apoptosis mediated by the mitochondrial pathway by a Bax/Bak-dependent mechanism. Here, we demonstrate that JNK phosphorylates two members of the BH3-only subgroup of Bcl2-related proteins (Bim and ...

Background/Aim: We have previously reported the identification of cytotoxic chemotype compound-I (CC-I) from a chemical library screening against glioblastoma. Materials and Methods: The biological activity CC-I on drug-resistant neuroblastomas [e.g., HFE gene variant C282Y stably transfected human neuroblastoma SH-SY5Y cells (C282Y HFE/SH-SY5Y), SK-N-AS] was characterized using cell culture mo...

The hematopoietic system plays a crucial role in immune defense response and normal development, it is regulated by various factors from other tissues. dysregulation of hematopoiesis associated with melanotic mass formation; however, the molecular mechanisms underlying this process are poorly understood. Here, we observed that overexpression miR-274 fat body resulted formation masses. Moreover,...

We previously reported that a small peptide based on amino acids 143-153 of the c-Jun N-terminal kinase (JNK)-binding domain of JIP-1 functioned as an in vitro inhibitor of JNK activity. This peptide (TI-JIP: RP-KRPTTLNLF) resembles the kinase-interaction motif (KIM = (K/R)(2-3)X(1-6)(L/I)X(L/I)), which is common to upstream activators, downstream substrates, phosphatases, and scaffold proteins...

We previously have shown that hypoxia increases the expression of P-glycoprotein, which in turn increases tumor cell capacity to actively extrude chemotherapeutic agents and may contribute to tumor drug resistance. This event is mediated through the hypoxia-inducible factor (HIF-1). Here, we investigated the role of the stress-activated protein kinase c-Jun NH(2)-terminal kinase (JNK) in the si...

We previously have shown that hypoxia increases the expression of P-glycoprotein, which in turn increases tumor cell capacity to actively extrude chemotherapeutic agents and may contribute to tumor drug resistance. This event is mediated through the hypoxia-inducible factor (HIF-1). Here, we investigated the role of the stress-activated protein kinase c-Jun NH2-terminal kinase (JNK) in the sign...

c-Jun NH(2)-terminal kinase (JNK) activation plays a major role in acetaminophen (APAP)-induced hepatotoxicity. However, the exact mechanism of APAP-induced JNK activation is incompletely understood. It has been established that apoptosis signal-regulating kinase 1 (ASK1) regulates the late phase of APAP-induced JNK activation, but the mitogen-activated protein kinase kinase kinase that mediate...

The Jun N-terminal kinase (JNK) is a downstream effector of Rac and Cdc42 GTPases involved in actin reorganization [1-3]. A role of the Drosophila JNK homologue, Basket (DJNK/Bsk), in the regulation of cell shape changes and actin reorganization arises from its function in the process of dorsal closure [4-6]. One potential mechanism for induction of cytoskeletal changes by JNK is via transcript...

BACKGROUND Glioblastoma multiforme is the most aggressive malignant primary brain tumor, characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Both PI3K/Akt and JNK pathways are essential to glioblastoma cell survival, migration and invasion. Due to their hyperactivation in glioblastoma cells, PI3K and JNK are promising targets for glioblastoma treatme...

Elevated endogenous JNK activity and resistance to Fas receptor-mediated apoptosis have recently been implicated in progression of prostate cancer and can promote resistance to apoptosis in response to chemotherapeutic drugs. In addition, JNK has been demonstrated to promote transformation of epithelial cells by increasing both proliferation and survival. Although numerous studies have reported...