Direct and indirect roles of cyclin-dependent kinase 5 as an upstream regulator in the c-Jun NH2-terminal kinase cascade: relevance to neurotoxic insults in Alzheimer's disease.


:Significant increase in JNK, c-Jun, and Cdk5 activities are reported in Alzheimer's disease (AD). Inhibition of c-Jun prevents neuronal cell death in in vivo AD models, highlighting it as a major JNK effector. Both JNK and Cdk5 promote neurodegeneration upon deregulation; however, Cdk5 has not been mechanistically linked to JNK or c-Jun. This study presents the first mechanism showing Cdk5 as a major regulator of the JNK cascade. Deregulated Cdk5 induces biphasic activation of JNK pathway. The first phase revealed c-Jun as a direct substrate of Cdk5, whose activation is independent of reactive oxygen species (ROS) and JNK. In the second phase, Cdk5 activates c-Jun via ROS-mediated activation of JNK. Rapid c-Jun activation is supported by in vivo data showing c-Jun phosphorylation in cerebral cortex upon p25 induction in transgenic mice. Cdk5-mediated biphasic activation of c-Jun highlights c-Jun, rather than JNK, as an important therapeutic target, which was confirmed in neuronal cells. Finally, Cdk5 inhibition endows superior protection against neurotoxicity, suggesting that Cdk5 is a preferable therapeutic target for AD relative to JNK and c-Jun.


Mol Biol Cell


Sun KH,Lee HG,Smith MA,Shah K




Has Abstract


2009-11-01 00:00:00














  • Two functionally identical modular enhancers in Drosophila troponin T gene establish the correct protein levels in different muscle types.

    abstract::The control of muscle-specific expression is one of the principal mechanisms by which diversity is generated among muscle types. In an attempt to elucidate the regulatory mechanisms that control fiber diversity in any given muscle, we have focused our attention on the transcriptional regulation of the Drosophila Tropo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Mas JA,García-Zaragoza E,Cervera M

    更新日期:2004-04-01 00:00:00

  • Enteropathogenic Escherichia coli subverts phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon epithelial cell infection.

    abstract::Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] are phosphoinositides (PIs) present in small amounts in the inner leaflet of the plasma membrane (PM) lipid bilayer of host target cells. They are thought to modulate the activity of proteins involved in en...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Sason H,Milgrom M,Weiss AM,Melamed-Book N,Balla T,Grinstein S,Backert S,Rosenshine I,Aroeti B

    更新日期:2009-01-01 00:00:00

  • The kinase activity of human Rio1 is required for final steps of cytoplasmic maturation of 40S subunits.

    abstract::RIO proteins form a conserved family of atypical protein kinases. Humans possess three distinct RIO kinases-hRio1, hRio2, and hRio3, of which only hRio2 has been characterized with respect to its role in ribosomal biogenesis. Here we show that both hRio1 and hRio3, like hRio2, are associated with precursors of 40S rib...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Widmann B,Wandrey F,Badertscher L,Wyler E,Pfannstiel J,Zemp I,Kutay U

    更新日期:2012-01-01 00:00:00

  • Systematic survey of deubiquitinase localization identifies USP21 as a regulator of centrosome- and microtubule-associated functions.

    abstract::Ubiquitination is a reversible modification that influences a broad range of physiological processes. There are approximately 90 deubiquitinases (DUBs) encoded in the human genome, of which 79 are predicted to have catalytic activity. We tagged 66 DUBs with green fluorescent protein and systematically surveyed their s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Urbé S,Liu H,Hayes SD,Heride C,Rigden DJ,Clague MJ

    更新日期:2012-03-01 00:00:00

  • Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins.

    abstract::More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot-Marie-Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To add...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: VanSlyke JK,Deschenes SM,Musil LS

    更新日期:2000-06-01 00:00:00

  • Integrin alpha 3 beta 1 participates in the phagocytosis of extracellular matrix molecules by human breast cancer cells.

    abstract::The mechanisms and receptors involved in phagocytosis by nonhematopoietic cells are not well understood. The involvement of the alpha 3 beta 1 integrin in phagocytosis of the extracellular matrix by human breast cancer cells was studied. The possible role of this integrin was suggested since alpha 3 and beta 1 but not...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Coopman PJ,Thomas DM,Gehlsen KR,Mueller SC

    更新日期:1996-11-01 00:00:00

  • Phosphorylation of the autoinhibitory domain of the Sso t-SNAREs promotes binding of the Vsm1 SNARE regulator in yeast.

    abstract::We have shown that protein kinase A phosphorylation of t-SNAREs inhibits SNARE assembly and suppresses endo- and exocytosis in yeast. Herein, we show that protein kinase A phosphorylation of the Sso exocytic t-SNAREs promotes the binding of Vsm1, a potential SNARE regulator identified previously in our laboratory. Pho...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Marash M,Gerst JE

    更新日期:2003-08-01 00:00:00

  • Differential phosphorylation signals control endocytosis of GPR15.

    abstract::GPR15 is an orphan G protein-coupled receptor (GPCR) that serves for an HIV coreceptor and was also recently found as a novel homing receptor for T-cells implicated in colitis. We show that GPR15 undergoes a constitutive endocytosis in the absence of ligand. The endocytosis was clathrin dependent and partially depende...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Okamoto Y,Shikano S

    更新日期:2017-08-15 00:00:00

  • Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast.

    abstract::In most eukaryotes, genes encoding ribosomal RNAs (rDNA) are clustered in long tandem head-to-tail repeats. Studies of Saccharomyces cerevisiae have indicated that rDNA copy number is maintained through recombination events associated with site-specific blockage of replication forks (RFs). Here, we describe two Schizo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Coulon S,Gaillard PHL,Chahwan C,McDonald WH,Yates JR 3rd,Russell P

    更新日期:2004-01-01 00:00:00

  • An ELMO2-RhoG-ILK network modulates microtubule dynamics.

    abstract::ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinoc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Jackson BC,Ivanova IA,Dagnino L

    更新日期:2015-07-15 00:00:00

  • Cdk5 Modulation of mitogen-activated protein kinase signaling regulates neuronal survival.

    abstract::Cdk5, a cyclin-dependent kinase, is critical for neuronal development, neuronal migration, cortical lamination, and survival. Its survival role is based, in part, on "cross-talk" interactions with apoptotic and survival signaling pathways. Previously, we showed that Cdk5 phosphorylation of mitogen-activated protein ki...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Zheng YL,Li BS,Kanungo J,Kesavapany S,Amin N,Grant P,Pant HC

    更新日期:2007-02-01 00:00:00

  • Cdc28 tyrosine phosphorylation and the morphogenesis checkpoint in budding yeast.

    abstract::A morphogenesis checkpoint in budding yeast delays nuclear division (and subsequent cell cycle progression) in cells that have failed to make a bud. We show that the ability of this checkpoint to delay nuclear division requires the SWE1 gene, encoding a protein kinase that inhibits the master cell cycle regulatory kin...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Sia RA,Herald HA,Lew DJ

    更新日期:1996-11-01 00:00:00

  • Beta 8 integrins mediate interactions of chick sensory neurons with laminin-1, collagen IV, and fibronectin.

    abstract::Integrins are major receptors used by cells to interact with extracellular matrices. In this paper, we identify the first ligands for the beta 8 family of integrins, presenting evidence that integrin heterodimers containing the beta 8 subunit mediate interactions of chick sensory neurons with laminin-1, collagen IV, a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Venstrom K,Reichardt L

    更新日期:1995-04-01 00:00:00

  • The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell-cell contacts.

    abstract::Despite the importance of epithelial cell contacts in determining cell behavior, we still lack a detailed understanding of the assembly and disassembly of intercellular contacts. Here we examined the role of the catalytic activity of the Src family kinases at epithelial cell contacts in vitro. Like E- and P-cadherin, ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Owens DW,McLean GW,Wyke AW,Paraskeva C,Parkinson EK,Frame MC,Brunton VG

    更新日期:2000-01-01 00:00:00

  • Cross talk between tetanus neurotoxin-insensitive vesicle-associated membrane protein-mediated transport and L1-mediated adhesion.

    abstract::The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells and hippocampal neurons in culture. TI-VAMP interacts with plasma membrane and e...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Alberts P,Rudge R,Hinners I,Muzerelle A,Martinez-Arca S,Irinopoulou T,Marthiens V,Tooze S,Rathjen F,Gaspar P,Galli T

    更新日期:2003-10-01 00:00:00

  • An aspartyl cathepsin, CTH3, is essential for proprotein processing during secretory granule maturation in Tetrahymena thermophila.

    abstract::In Tetrahymena thermophila, peptides secreted via dense-core granules, called mucocysts, are generated by proprotein processing. We used expression profiling to identify candidate processing enzymes, which localized as cyan fluorescent protein fusions to mucocysts. Of note, the aspartyl cathepsin Cth3p plays a key rol...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Kumar S,Briguglio JS,Turkewitz AP

    更新日期:2014-08-15 00:00:00

  • Up-regulation of BMP2/4 signaling increases both osteoblast-specific marker expression and bone marrow adipogenesis in Gja1Jrt/+ stromal cell cultures.

    abstract::Gja1(Jrt)/+ mice carry a mutation in one allele of the gap junction protein α1 gene (Gja1), resulting in a G60S connexin 43 (Cx43) mutant protein that is dominant negative for Cx43 protein production of <50% of wild-type (WT) levels and significantly reduced gap junction formation and function in osteoblasts and other...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Zappitelli T,Chen F,Aubin JE

    更新日期:2015-03-01 00:00:00

  • What makes the cell cycle tick? a celebration of the awesome power of biochemistry and the frog egg.

    abstract::The cell cycle, a 19th century discovery of cytologists, only achieved a satisfactory biochemical explanation in the last 20 years of the 20th century. This personal retrospective focuses on how biochemical studies of the frog egg helped identify the cyclin-based mitotic oscillator and how this approach quickly merged...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Kirschner M

    更新日期:2020-12-15 00:00:00

  • Orientational order of the lamellipodial actin network as demonstrated in living motile cells.

    abstract::Lamellipodia of crawling cells represent both the motor for cell advance and the primary building site for the actin cytoskeleton. The organization of actin in the lamellipodium reflects actin dynamics and is of critical importance for the mechanism of cell motility. In previous structural studies, the lamellipodial a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Verkhovsky AB,Chaga OY,Schaub S,Svitkina TM,Meister JJ,Borisy GG

    更新日期:2003-11-01 00:00:00

  • Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration.

    abstract::The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions di...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Bernis C,Swift-Taylor B,Nord M,Carmona S,Chook YM,Forbes DJ

    更新日期:2014-04-01 00:00:00

  • Distinct FTDP-17 missense mutations in tau produce tau aggregates and other pathological phenotypes in transfected CHO cells.

    abstract::Multiple tau gene mutations are pathogenic for hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), with filamentous tau aggregates as the major lesions in the CNS of these patients. Recent studies have shown that bacterially expressed recombinant tau proteins with FTDP-17 missense mu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Vogelsberg-Ragaglia V,Bruce J,Richter-Landsberg C,Zhang B,Hong M,Trojanowski JQ,Lee VM

    更新日期:2000-12-01 00:00:00

  • Budding yeast Dma1 and Dma2 participate in regulation of Swe1 levels and localization.

    abstract::Timely down-regulation of the evolutionarily conserved protein kinase Swe1 plays an important role in cell cycle control, as Swe1 can block nuclear division through inhibitory phosphorylation of the catalytic subunit of cyclin-dependent kinase. In particular, Swe1 degradation is important for budding yeast cell surviv...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Raspelli E,Cassani C,Lucchini G,Fraschini R

    更新日期:2011-07-01 00:00:00

  • A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression.

    abstract::Lactogenic hormones and extracellular matrix (ECM) act synergistically to regulate beta-casein expression in culture. We have developed a functional subpopulation of the mouse mammary epithelial cell strain COMMA-1D (designated CID 9), which expresses high level of beta-casein, forms alveolar-like structures when plat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Schmidhauser C,Casperson GF,Myers CA,Sanzo KT,Bolten S,Bissell MJ

    更新日期:1992-06-01 00:00:00

  • Sec24C/D-isoform-specific sorting of the preassembled ER-Golgi Q-SNARE complex.

    abstract::Secretory proteins are exported from the endoplasmic reticulum in COPII vesicles. SNARE proteins-core machinery for membrane fusion-are incorporated into COPII vesicles by direct interaction with Sec24. Here we report a novel mechanism for sorting of the ER-Golgi Q-SNAREs into COPII vesicles. Different mammalian Sec24...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Adolf F,Rhiel M,Reckmann I,Wieland FT

    更新日期:2016-09-01 00:00:00

  • GLUT1CBP(TIP2/GIPC1) interactions with GLUT1 and myosin VI: evidence supporting an adapter function for GLUT1CBP.

    abstract::We identified a novel interaction between myosin VI and the GLUT1 transporter binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it might function to couple vesicle-bound proteins to myosin VI movement. This study refines the model by identifying two myosin VI binding domains in the GIPC1 C...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Reed BC,Cefalu C,Bellaire BH,Cardelli JA,Louis T,Salamon J,Bloecher MA,Bunn RC

    更新日期:2005-09-01 00:00:00

  • Modulation of myoblast fusion by caveolin-3 in dystrophic skeletal muscle cells: implications for Duchenne muscular dystrophy and limb-girdle muscular dystrophy-1C.

    abstract::Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Volonte D,Peoples AJ,Galbiati F

    更新日期:2003-10-01 00:00:00

  • Rab GDI: a solubilizing and recycling factor for rab9 protein.

    abstract::Rab proteins are thought to function in the processes by which transport vesicles identify and/or fuse with their respective target membranes. The bulk of these proteins are membrane associated, but a measurable fraction can be found in the cytosol. The cytosolic forms of rab3A, rab11, and Sec4 occur as equimolar comp...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Soldati T,Riederer MA,Pfeffer SR

    更新日期:1993-04-01 00:00:00

  • Differential modulation of cadherin-mediated cell-cell adhesion by platelet endothelial cell adhesion molecule-1 isoforms through activation of extracellular regulated kinases.

    abstract::The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in endothelial cell-cell interactions and its contribution to cadherin-mediated cell adhesion are poorly understood. Such studies have been difficult because all known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney (MDCK) ce...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Sheibani N,Sorenson CM,Frazier WA

    更新日期:2000-08-01 00:00:00

  • Swi5 controls a novel wave of cyclin synthesis in late mitosis.

    abstract::We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Aerne BL,Johnson AL,Toyn JH,Johnston LH

    更新日期:1998-04-01 00:00:00

  • EDEM is involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol.

    abstract::The plant toxin ricin is transported retrogradely from the cell surface to the endoplasmic reticulum (ER) from where the enzymatically active part is retrotranslocated to the cytosol, presumably by the same mechanism as used by misfolded proteins. The ER degradation enhancing alpha-mannosidase I-like protein, EDEM, is...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章


    authors: Slominska-Wojewodzka M,Gregers TF,Wälchli S,Sandvig K

    更新日期:2006-04-01 00:00:00