Rb protein down-regulates the stress-activated signals through inhibiting c-Jun N-terminal kinase/stress-activated protein kinase. 2000

J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
National Creative Research Initiative Center for Cell Death, Graduate School of Biotechnology, Korea University, Seoul, 136-701, Korea.

The Rb protein is the product of the retinoblastoma susceptibility gene and loss of Rb function is detected in many types of human cancers. Rb plays important roles in the regulation of cell proliferation, differentiation, senescence, and apoptotic cell death. Here we show that Rb can physically interact with c-Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK), thereby inhibiting intracellular signals mediated by JNK/SAPK. Both in vitro binding and in vitro kinase studies suggest that a carboxyl-terminal domain of Rb containing amino acids 768-928 might be crucial for inhibiting JNK/SAPK. In comparison, Rb did not affect enzymatic activity of either extracellular signal-regulated kinase 1 or p38. Ectopically expressed Rb also abrogated the apoptotic cell death induced by ultraviolet radiation or the activation of MEKK1, an upstream kinase that can stimulate the JNK/SAPK cascade. JNK/SAPK inhibition highlights a novel function of Rb, which may provide a new mechanism by which Rb regulates cell death. JNK/SAPK is a major protein kinase that can be stimulated in response to a variety of cellular stresses. Our results, therefore, suggest that Rb, by inhibiting JNK/SAPK, may act as a negative regulator in stress-activated intracellular signaling cascades.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016160 Retinoblastoma Protein Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. Rb Protein,Retinoblastoma Nuclear Phosphoprotein p105-Rb,p105-Rb Protein,Rb Gene Product,Rb1 Gene Product,Retinoblastoma Nuclear Phosphoprotein p105 Rb,p105 Rb Protein
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D048055 Mitogen-Activated Protein Kinase 8 A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING. JNK1 Kinase,MAPK8 Mitogen-Activated Protein Kinase,SAP Kinase-1,SAPK1 Mitogen-Activated Protein Kinase,Stress-Activated Protein Kinase 1,Stress-Activated Protein Kinase JNK1,Stress-Activated Protein Kinase gamma,c-jun Kinase-1,c-jun N-Terminal Kinase 1,MAPK8 Mitogen Activated Protein Kinase,Mitogen Activated Protein Kinase 8,SAP Kinase 1,SAPK1 Mitogen Activated Protein Kinase,Stress Activated Protein Kinase 1,Stress Activated Protein Kinase JNK1,Stress Activated Protein Kinase gamma,c jun Kinase 1,c jun N Terminal Kinase 1
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

Related Publications

J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
November 1997, Biochemistry,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
April 1997, Journal of neurochemistry,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
February 2000, Chang Gung medical journal,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
December 2000, Proceedings of the National Academy of Sciences of the United States of America,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
April 2002, Oncogene,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
March 1997, The Journal of biological chemistry,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
January 2000, The Journal of biological chemistry,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
October 1996, Journal of neuroscience research,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
October 1998, The Journal of biological chemistry,
J Shim, and H S Park, and M J Kim, and J Park, and E Park, and S G Cho, and S J Eom, and H W Lee, and C O Joe, and E J Choi
September 2002, Journal of immunology (Baltimore, Md. : 1950),
Copied contents to your clipboard!