- Wiley Online Library
... selectivity and, thus, in cell fate decision. In support of this model, additional kinases have been shown to phosphorylate p53 on Ser 46 and to have a role in p53-mediated apoptosis. For example, the homeodomain -interacting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, phosphoryl ...
... selectivity and, thus, in cell fate decision. In support of this model, additional kinases have been shown to phosphorylate p53 on Ser 46 and to have a role in p53-mediated apoptosis. For example, the homeodomain -interacting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, phosphoryl ...
Two-step and one-step secretion mechanisms in Gram
... Every pilus subunit possesses a 10–20 residue long disordered Nte (N-terminal extension), which, similar to the G1 β-strand of the chaperone, contains alternating hydrophobic residues. This Nte was shown not to be part of the Ig-like fold [36]. During the course of polymerization, the Nte of the inc ...
... Every pilus subunit possesses a 10–20 residue long disordered Nte (N-terminal extension), which, similar to the G1 β-strand of the chaperone, contains alternating hydrophobic residues. This Nte was shown not to be part of the Ig-like fold [36]. During the course of polymerization, the Nte of the inc ...
Nuclear and Nucleolar Localization by the N
... 36). In yeast, expression of human topo I is unhealthy and its overexpression is lethal but also dependent on the N-terminal domain (3). Most likely the N-terminus functions in nuclear targeting and since the 166-210-amino acid region of human topo I can form a complex with nucleolin, a possible mec ...
... 36). In yeast, expression of human topo I is unhealthy and its overexpression is lethal but also dependent on the N-terminal domain (3). Most likely the N-terminus functions in nuclear targeting and since the 166-210-amino acid region of human topo I can form a complex with nucleolin, a possible mec ...
Regulation of phospholipase D activity, membrane targeting and
... regulator of both constitutive and agonist-promoted intracellular vesicle trafficking [1,2]. Several recent reviews discuss the structure, regulation and functions of PLD. This short article focuses on the role of phosphoinositides as regulators of yeast and mammalian PLD activity and function and, ...
... regulator of both constitutive and agonist-promoted intracellular vesicle trafficking [1,2]. Several recent reviews discuss the structure, regulation and functions of PLD. This short article focuses on the role of phosphoinositides as regulators of yeast and mammalian PLD activity and function and, ...
Regulation of mTORC1 by amino acids
... reducing the levels of lysosomal v-ATPase components severely inhibits dTORC1 signaling. Complementing the RNAi results, the use of v-ATPase-specific chemical inhibitors in mammalian cells verified the importance of this complex in mediating the amino acid signal to mTORC1. The v-ATPase is composed ...
... reducing the levels of lysosomal v-ATPase components severely inhibits dTORC1 signaling. Complementing the RNAi results, the use of v-ATPase-specific chemical inhibitors in mammalian cells verified the importance of this complex in mediating the amino acid signal to mTORC1. The v-ATPase is composed ...
Identification of an estrogen receptor a non covalent ubiquitin
... ubiquitinated species from total cellular lysates (Fig. 1A). Because the A/B domain is non-structured and displays weak association to ubiquitinated species when compared to the 12 ahelix-containing E domain, we focused on the E domain Ubbinding ability. Fig. 1B shows that this receptor portion is a ...
... ubiquitinated species from total cellular lysates (Fig. 1A). Because the A/B domain is non-structured and displays weak association to ubiquitinated species when compared to the 12 ahelix-containing E domain, we focused on the E domain Ubbinding ability. Fig. 1B shows that this receptor portion is a ...
Fig. 1 - The Journal of Cell Biology
... Tim23 pore. A surprising and still unresolved observation is that a loss of Tim50 leads to robust import defects for matrix proteins, but has a much lesser effect on precursors sorted into the inner membrane (Geissler et al., 2002). To assess the function of Tim50 in protein transport, we isolated m ...
... Tim23 pore. A surprising and still unresolved observation is that a loss of Tim50 leads to robust import defects for matrix proteins, but has a much lesser effect on precursors sorted into the inner membrane (Geissler et al., 2002). To assess the function of Tim50 in protein transport, we isolated m ...
Structural Studies of Human 5’-Nucleotidases Karin Walldén
... chemical reactions. Some enzymes degrade components of food and channel the energy released by this process into chemical energy in the form of for instance the nucleotide ATP. Other enzymes can then use ATP as energy source for synthesis of various components of the cell. The degradation (catabolis ...
... chemical reactions. Some enzymes degrade components of food and channel the energy released by this process into chemical energy in the form of for instance the nucleotide ATP. Other enzymes can then use ATP as energy source for synthesis of various components of the cell. The degradation (catabolis ...
Animal mitochondrial biogenesis and function
... that these two proteins are involved in mtDNA stability. Surprisingly, Hsp60p is a single-stranded DNA binding protein that binds speci®cally to a putative origin of mtDNA replication. The mitochondrial genome is replicated and transcribed within the organelle. Both mtDNA replication and transcripti ...
... that these two proteins are involved in mtDNA stability. Surprisingly, Hsp60p is a single-stranded DNA binding protein that binds speci®cally to a putative origin of mtDNA replication. The mitochondrial genome is replicated and transcribed within the organelle. Both mtDNA replication and transcripti ...
The AMP-activated protein kinase pathway – new
... closely together through hydrophobic interactions. As it is now clear that the basic functional unit is a dimer, Kemp has suggested the term ‘Bateman domain’ to refer to the structure formed by two tandem repeats (Kemp, 2004). Initially, the function(s) of Bateman domains was not known, but recent s ...
... closely together through hydrophobic interactions. As it is now clear that the basic functional unit is a dimer, Kemp has suggested the term ‘Bateman domain’ to refer to the structure formed by two tandem repeats (Kemp, 2004). Initially, the function(s) of Bateman domains was not known, but recent s ...
AMP-activated/SNF1 protein kinases: conserved guardians of
... know almost nothing about the properties of the enzyme from S. pombe, but this structure does define the core interactions between the three subunits, which are likely to be conserved between different eukaryotes. The α-subunits: catalytic subunits. Two α-subunit iso forms (α1/α2) are encoded by di ...
... know almost nothing about the properties of the enzyme from S. pombe, but this structure does define the core interactions between the three subunits, which are likely to be conserved between different eukaryotes. The α-subunits: catalytic subunits. Two α-subunit iso forms (α1/α2) are encoded by di ...
Identification of Plasmodium falciparum var1CSA
... affinity-purified goat polyclonal anti-human IgM reagent (Rockland, Gilbertsville, PA, USA, data not shown). For the var2CSA gene, each domain was also expressed at the surface of the COS7 cells. Again, only one construct, the DBL6 domain, gave a positive result for human IgM binding (Table 1 and F ...
... affinity-purified goat polyclonal anti-human IgM reagent (Rockland, Gilbertsville, PA, USA, data not shown). For the var2CSA gene, each domain was also expressed at the surface of the COS7 cells. Again, only one construct, the DBL6 domain, gave a positive result for human IgM binding (Table 1 and F ...
Death of developing neurons: New insights and implications for
... neuron to undergo apoptosis seems to be determined by a tightly regulated apoptotic machinery (summarized in Fig. 1). Therefore, modulation of the expression levels or the activity of components of this apoptotic balance changes the sensitivity to deathpromoting cues, allowing temporal restriction o ...
... neuron to undergo apoptosis seems to be determined by a tightly regulated apoptotic machinery (summarized in Fig. 1). Therefore, modulation of the expression levels or the activity of components of this apoptotic balance changes the sensitivity to deathpromoting cues, allowing temporal restriction o ...
PDF - The Journal of Cell Biology
... activates JNK, causing apoptosis, but its expression can also be activated by JNK to induce nonapoptotic cell death (Liu et al., 2015; Wu et al., 2015a,b). Toll-2, -3, -8, and -9 can induce apoptosis via NF-κB and dSarm independently of MyD88 and JNK (Meyer et al., 2014). However, in the CNS, dSarm ...
... activates JNK, causing apoptosis, but its expression can also be activated by JNK to induce nonapoptotic cell death (Liu et al., 2015; Wu et al., 2015a,b). Toll-2, -3, -8, and -9 can induce apoptosis via NF-κB and dSarm independently of MyD88 and JNK (Meyer et al., 2014). However, in the CNS, dSarm ...
Small-molecule binding sites to explore new targets in the cancer
... The transcription factor HNF4A forms a homodimer complex to interact with DNA to control the expression of other genes. In the monomer structure, two binding sites were detected on the protein surface (Fig. S5D). One of these two sites is bound to a saturated fatty acid in multiple superimposed crys ...
... The transcription factor HNF4A forms a homodimer complex to interact with DNA to control the expression of other genes. In the monomer structure, two binding sites were detected on the protein surface (Fig. S5D). One of these two sites is bound to a saturated fatty acid in multiple superimposed crys ...
Cardiolipin-Mediated Mitochondrial Dynamics and
... yeasts by enhancing the organization, stabilization, and/or activity of several protein complexes involved in respiration and protein import (Osman et al., 2011). CL also regulates the early events of apoptotic programmed cell death (PCD) in animals by providing an activating platform for Bcl-2 fami ...
... yeasts by enhancing the organization, stabilization, and/or activity of several protein complexes involved in respiration and protein import (Osman et al., 2011). CL also regulates the early events of apoptotic programmed cell death (PCD) in animals by providing an activating platform for Bcl-2 fami ...
The Nucleolus under Stress
... composition of the nucleolus (Table 1). A well-described phenomenon is the nucleolar segregation caused by DNA damage (e.g., following UV irradiation or inhibition of topoisomerase II by drugs such as etoposide) and/or transcriptional inhibition (e.g., by actinomycin D) (Al-Baker et al., 2005; Govon ...
... composition of the nucleolus (Table 1). A well-described phenomenon is the nucleolar segregation caused by DNA damage (e.g., following UV irradiation or inhibition of topoisomerase II by drugs such as etoposide) and/or transcriptional inhibition (e.g., by actinomycin D) (Al-Baker et al., 2005; Govon ...
Adherens Junctions, Desmosomes and Tight
... membrane. This includes transmembrane and intracellular portions of cell-cell junctions. Thus, desmosomes can no longer be recycled and, from that level on, their destiny is to be degraded by adequate hydrolases. In the horny layer, the morphology of desmosomes changes dramatically. The layered stru ...
... membrane. This includes transmembrane and intracellular portions of cell-cell junctions. Thus, desmosomes can no longer be recycled and, from that level on, their destiny is to be degraded by adequate hydrolases. In the horny layer, the morphology of desmosomes changes dramatically. The layered stru ...
Cytochrome c Release and Apoptosis Induced by Mitochondrial
... Repression of TR3 transactivation function by these apoptosis inducers was unexpected, because TR3 was thought to exert its proapoptotic effect by acting as a transcription factor to regulate gene expression (13– 16). Repression of TR3 transactivation was not related to direct binding of apoptosis i ...
... Repression of TR3 transactivation function by these apoptosis inducers was unexpected, because TR3 was thought to exert its proapoptotic effect by acting as a transcription factor to regulate gene expression (13– 16). Repression of TR3 transactivation was not related to direct binding of apoptosis i ...
PROTEIN DEPHOSPHORYLATION AND THE INTRACELLULAR
... inhibition). Long-term treatment of cells with low OA concentrations makes them resistant to OA: Remarkably, this is associated with a point mutation in PP2A (C269G) that increases its IC50 about fourfold (38). This suggests that the primary target of OA action may be PP2A. Of course, this does not ...
... inhibition). Long-term treatment of cells with low OA concentrations makes them resistant to OA: Remarkably, this is associated with a point mutation in PP2A (C269G) that increases its IC50 about fourfold (38). This suggests that the primary target of OA action may be PP2A. Of course, this does not ...
Inhibition of Protein Kinases by Balanol: Specificity within the Serine
... Fig. 2B). The Ki values for 140-decarboxybalanol and 100deoxybalanol on PKA are 11 and 3.9 nM (Koide et al., 1995). Thus, eliminating the seven-membered ring from balanol backbone has a modest effect on balanol’s affinity toward the ATP binding site on PKA, whereas omission of the carboxy or hydroxy ...
... Fig. 2B). The Ki values for 140-decarboxybalanol and 100deoxybalanol on PKA are 11 and 3.9 nM (Koide et al., 1995). Thus, eliminating the seven-membered ring from balanol backbone has a modest effect on balanol’s affinity toward the ATP binding site on PKA, whereas omission of the carboxy or hydroxy ...
Energetic Crosstalk Between Organelles
... the hydrolysis of ATP catalyzed by the cellular ATPases.1 SR load was up to 4-fold more effective when ATP was used instead of ADP (Figure 1, right). Moreover, when mitochondria were blocked with 2 mmol/L sodium azide, only 5% of the response remained, suggesting that most of the ATP used was of mit ...
... the hydrolysis of ATP catalyzed by the cellular ATPases.1 SR load was up to 4-fold more effective when ATP was used instead of ADP (Figure 1, right). Moreover, when mitochondria were blocked with 2 mmol/L sodium azide, only 5% of the response remained, suggesting that most of the ATP used was of mit ...
Energetic Crosstalk Between Organelles
... the hydrolysis of ATP catalyzed by the cellular ATPases.1 SR load was up to 4-fold more effective when ATP was used instead of ADP (Figure 1, right). Moreover, when mitochondria were blocked with 2 mmol/L sodium azide, only 5% of the response remained, suggesting that most of the ATP used was of mit ...
... the hydrolysis of ATP catalyzed by the cellular ATPases.1 SR load was up to 4-fold more effective when ATP was used instead of ADP (Figure 1, right). Moreover, when mitochondria were blocked with 2 mmol/L sodium azide, only 5% of the response remained, suggesting that most of the ATP used was of mit ...
The unfolded protein response: controlling cell fate
... the transcription of genes encoding proteins involved in protein folding, ER-associated degradation (ERAD), protein quality control and phospholipid synthesis. IRE1α also degrades certain mRNAs through regulated IRE1‑dependent decay (RIDD) and induces ‘alarm stress pathways’, including those driven ...
... the transcription of genes encoding proteins involved in protein folding, ER-associated degradation (ERAD), protein quality control and phospholipid synthesis. IRE1α also degrades certain mRNAs through regulated IRE1‑dependent decay (RIDD) and induces ‘alarm stress pathways’, including those driven ...
For unknown reasons, p21 expression induces different effects in
... constant DNA damage response responsible for the prolonged cell cycle arrest (19). p21 prevents cancer cell growth due to its ability to transiently or permanently stop proliferation, thus being an important component of tumour suppressor mechanisms. Indeed, it has recently been shown that p21 can b ...
... constant DNA damage response responsible for the prolonged cell cycle arrest (19). p21 prevents cancer cell growth due to its ability to transiently or permanently stop proliferation, thus being an important component of tumour suppressor mechanisms. Indeed, it has recently been shown that p21 can b ...
Apoptosome
The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death stimulus. Stimuli can vary from DNA damage and viral infection to developmental cues such as those leading to the degradation of a tadpole's tail.In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of apoptosome. An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. However, recent structural studies suggest the cytochrome c to apaf-1 ratio is one-to-one. It has also been shown that the nucleotide dATP as third component binds to apaf-1, however its exact role is still debated. The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic transmission electron microscopy 10 years ago, revealing a wheel-like particle with 7-fold symmetry. Recently, a medium resolution (9.5 Ångström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. There is also now a crystal structure of the monomeric, inactive Apaf-1 subunit (PDB 3SFZ). Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis.