Identification of the Critical Features of a Small Peptide Inhibitor of JNK Activity

Barr, Renae K.; Kendrick, Tulene S.; Bogoyevitch, Marie A.

doi:10.1074/jbc.m107565200

Cited by 200 publications

(227 citation statements)

References 45 publications

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“…28 Conversely, overexpression of IB1/JIP-1 or the use of small JNK-inhibitory peptides could prevent the proapoptotic signalling cascade. [29][30][31] In humans, a single missense mutation was identified in the coding region of the MAPK8IP1 gene. 32 This mutation is associated with a rare form of late-onset, monogenic form of type II diabetes and in vitro an accelerated apoptosis of the insulin-secreting cells.…”

Section: Introductionmentioning

confidence: 99%

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

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Islet-brain1 (IB1) or c-Jun NH2 terminal kinase interacting protein-1 (JIP-1), the product of the MAPK8IP1 gene, functions as a neuronal scaffold protein to allow signalling specificity. IB1/ JIP-1 interacts with many cellular components including the reelin receptor ApoER2, the lowdensity lipoprotein receptor-related protein (LRP), kinesin and the Alzheimer's amyloid precursor protein. Coexpression of IB1/JIP-1 with other components of the c-Jun NH2 terminal-kinase (JNK) pathway activates the JNK activity; conversely, selective disruption of IB1/JIP-1 in mice reduces the stress-induced apoptosis of neuronal cells. We therefore hypothesized that IB1/JIP-1 is a risk factor for Alzheimer's disease (AD). By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles. We next identified a À499A4G polymorphism in the 5' regulatory region of the MAPK8IP1 gene. In two separate French populations the À499A4G polymorphism of MAPK8IP1 was not associated with an increased risk to AD. However, when stratified on the þ 766C4T polymorphism of exon 3 of the LRP gene, the IB1/JIP-1 polymorphism was strongly associated with AD in subjects bearing the CC genotype in the LRP gene. The functional consequences of the -499A4G polymorphism of MAPK8IP1 was investigated in vitro. In neuronal cells, the G allele increased transcriptional activity and was associated with an enhanced binding activity. Taken together, these data indicate that the increased transcriptional activity in the presence of the G allele of MAPK8IP1 is a risk factor to the onset of in patients bearing the CC genotype of the LRP gene.

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Section: Introductionmentioning

confidence: 99%

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

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“…p38 inhibitor, SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) 1 H-imidazole], and JNK-1 inhibitory peptide H-GRKKRRQRRRPPRPKRPTTLNLFPQVPRSQDT-NH2 [ L-HIV-TAT 48-57 PP-JBD 20 ] were purchased from Calbiochem (LaJolla, CA). The concentration of inhibitors, 20μM was selected based on published studies (7,20). In other experiments cells were treated with 50μM inhibitors to caspase-3 (Z-DEVD-FMK), caspase-8 (Z-IETD-FMK) or caspase-9 (Z-LEHD-FMK) at the time of CML-collagen stimulation.…”

Section: Apoptosis Assaymentioning

confidence: 99%

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Alikhani

Boyd

et al. 2007

Bone

321

220

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We have previously shown that diabetes significantly enhances apoptosis of osteoblastic cells in vivo and that the enhanced apoptosis contributes to diabetes impaired new bone formation. A potential mechanism is enhanced apoptosis stimulated by advanced glycation endproducts (AGEs). To investigate this further, an advanced glycation product, carboxymethyl lysine modified collagen (CML-collagen) was injected in vivo and stimulated a 5 fold increase in calvarial periosteal cell apoptosis compared to unmodified collagen. It also induced apoptosis in primary cultures of human or neonatal rat osteoblastic cells or MC-3T3-E1 cells in vitro. Moreover, the apoptotic effect was largely mediated through RAGE receptor. CML-collagen increased p38 and JNK activity 3.2 and 4.4 fold, respectively. Inhibition of p38 and JNK reduced CML-collagen stimulated apoptosis by 45% and 59% and by 90% when used together (P<0.05). The predominant apoptotic pathway induced by CML-collagen involved caspase-8 activation of caspase-3 and was independent of NF-κB activation. When osteoblastic cells were exposed to a long-term low dose incubation with CMLcollagen there was a higher degree of apoptosis compared to short term incubation. In more differentiated osteoblastic cultures apoptosis was enhanced even further. These results indicate that advanced glycation endproducts, which accumulate in diabetic and aged individuals may promote apoptosis of osteoblastic cells and contribute to deficient bone formation.

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“…One of the most selective JNK inhibitors currently available is the JNK-inhibitory peptide analogue, L/D-JNKI (Barr et al, 2002) and thus was chosen to inhibit JNK to examine the role of JNK in TRAIL-induced colon carcinoma cell apoptosis. Inhibition of JNK by L-JNKI was confirmed by measuring JNK activity in TRAIL-and UV-treated HCT15 cells with an in vitro kinase assay ( Figure 3A).…”

Section: Colo205 Hct15 and Hca7 Colon Cancer Cells Are Sensitive To mentioning

confidence: 99%

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

et al. 2009

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Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis on binding to its receptors, death receptor 4 and 5 (DR4, DR5). TRAIL can also activate c-Jun N-terminal kinase (JNK) through the adaptor molecules, TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP). The role of JNK in TRAIL-induced tumour cell apoptosis is unclear. In this study, we demonstrate that JNK is activated by TRAIL in colon cancer cells. Inhibition of JNK with L-JNKI reduced rhTRAIL-induced cell death but enhanced cell death induced by selective activation of DR4 or DR5. This difference was unrelated to receptor internalisation or differential activation of c-Jun, but activation of different JNK isoforms. Our data demonstrate that JNK1, but not JNK2 is activated by rhTRAIL in the examined colon cancer cell lines. Although rhTRAIL activated both the long and short isoforms of JNK1, selective activation of DR4 or DR5 led to predominant activation of the short JNK1 isoforms (JNK1a1 and/or JNK1b1). Knockdown of JNK1a1 by shRNA enhanced apoptosis induced by TRAIL, agonistic DR4 or DR5 antibodies. On the other hand, knockdown of the long JNK1 isoforms (JNK1a2 and JNK1b2) had the opposite effect; it reduced TRAIL-induced cell death. These data indicate that the short JNK1 isoforms transmit an antiapoptotic signal, whereas the long isoforms (JNK1a2 or JNK1b2) act in a proapoptotic manner.

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Identification of the Critical Features of a Small Peptide Inhibitor of JNK Activity

Cited by 200 publications

References 45 publications

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines

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