c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for mitoxantrone- and anisomycin-induced apoptosis in HL-60 cells

Stadheim, Terrance A.; Kucera, Gregory L.

doi:10.1016/s0145-2126(01)00099-6

Cited by 104 publications

(73 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Likewise, recent reports have described a requirement for JNK/SAPK, but not p38 in both mitoxantrone-and anisomycin-induced apoptosis in HL-60 promyelocytic leukemia cells. 19 These findings, however, can also be viewed in the light of previous reports characterizing p38 as an important mediator in the production of proinflammatory and/or pyrogenic cytokines (eg, IL-6, IL-1b, and TNFa). [20][21][22] Together with the observed disparities between JNK1/JNK2 and p38 signaling in apoptotic commitment, it may be that p38 represents a signal for priming an apoptotic response rather than subserving a role as a direct throughput apparatus in the initiation of cell death.…”

Section: Discussionsupporting

confidence: 53%

Requirement for SAPK–JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells

et al. 2003

View full text Add to dashboard Cite

The present studies examined performance of SAPK cascades and apoptotic commitment following ribosomal trauma in REH lymphoid leukemia cells. Ribostatic insults included disruption of ribosomal activity by mechanistically dissimilar agents such as blasticidin-S (BCS) (which binds 28S-rRNA to block peptidyl bond formation), kasugamycin (KSM) (which binds 18S-rRNA to prevent translational initiation), and cycloheximide (CHX) (which blocks A-site to P-site translocation of peptidyl-tRNA). Exposure of REH cells to BCS elicited DNA degradation and apoptotic cytolysis. BCS stimulated JNK1/JNK2 and p38, and their shared targets c-Jun and ATF2. Inhibition of JNK1/JNK2 (but not of p38) antagonized blasticidin-induced apoptosis, whereas targeting alternative ribosomal sites with KSM or CHX limited translation, but failed to activate the SAPK cascade or initiate apoptosis. Our findings indicate that interference with 28S-rRNA by BCS initiates apoptosis in REH cells through recruitment of SAPK-JNK signaling. Disparities between the lethal actions of BCS, KSM, and CHX appear to reflect established differences in the subribosomal targets of these agents. We propose that the SAPK cascade comprises an essential mechanism for the transduction of specific lethal stress signals emanating from active ribosomes, and that interference with the 28S-rRNA, rather than the peptidyl transfer center of the large subunit, is critical to apoptotic commitment.

show abstract

Section: Discussionsupporting

confidence: 53%

Requirement for SAPK–JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Several reports provide evidence that JNKs function as proapoptotic kinases in response to various stimuli (6)(7)(8)(9)(10)(11). The JNK pathways activate caspases and may also target other factors implicated in mitochondrial apoptotic cell death regulation, including p53, Bcl-2, and Bax (27).…”

Section: Discussionmentioning

confidence: 99%

“…The ERK pathway, activated by mitogenic stimuli such as growth factors, cytokines, and phorbol esters, plays a major role in regulating cell growth, survival, and differentiation (1)(2)(3)(4)(5). In contrast, JNK and p38 MAPK are weakly activated by growth factors, but respond strongly to stress signals including tumor necrosis factor, interleukin-1, ionizing and UV irradiation, hyperosmotic stress, and chemotherapeutic drugs (6)(7)(8)(9)(10)(11). Activation of these kinases is strongly associated with apoptotic cell death induced by stress stimuli.…”

Section: Introductionmentioning

confidence: 99%

Opposing Roles of c-Jun NH2-Terminal Kinase and p38 Mitogen-Activated Protein Kinase in the Cellular Response to Ionizing Radiation in Human Cervical Cancer Cells

Kim

Choi

Park

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

Exposure of cells to ionizing radiation induces activation of multiple signaling pathways that play critical roles in determining cell fate. However, the molecular basis for cell death or survival signaling in response to radiation is unclear at present. Here, we show opposing roles of the c-jun NH 2 -terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways in the mitochondrial cell death in response to ionizing radiation in human cervical cancer cells. Ionizing radiation triggered Bax and Bak activation, Bcl-2 down-regulation, and subsequent mitochondrial cell death. Inhibition of JNK completely suppressed radiation-induced Bax and Bak activation and Bcl-2 down-regulation. Dominant-negative forms of stress-activated protein kinase/extracellular signal-regulated kinase kinase 1 (SEK-1)/mitogen-activated protein kinase kinase-4 (MKK-4) inhibited JNK activation. Radiation also induced phosphoinositide 3-kinase (PI3K) activation. Interestingly, inhibition of PI3K effectively attenuated radiation-induced mitochondrial cell death and increased clonogenic survival. Inhibition of PI3K also suppressed SEK-1/MKK-4 and JNK activation, Bax and Bak activation, and Bcl-2 down-regulation. In contrast, inhibition of p38 MAPK led to enhanced Bax and Bak activation and mitochondrial cell death. RacN17, a dominant-negative form of Rac1, inhibited p38 MAPK activation and increased Bax and Bak activation. Exposure of cells to radiation also induced selective activation of c-Src among Src family kinases. Inhibition of c-Src by pretreatment with Src family kinase inhibitor PP2 or small interfering RNA targeting of c-Src attenuated radiation-induced p38 MAPK and Rac1 activation and enhanced Bax and Bak activation and cell death. Our results support the notion that the PI3K-SEK-1/MKK-4-JNK pathway is required for the mitochondrial cell death in response to radiation, whereas the c-Src-Rac1-p38 MAPK pathway plays a cytoprotective role against mitochondrial cell death.

show abstract

“…In addition to activate JNK1, anisomycin inhibits protein synthesis and mediates apoptosis (23,24). Anisomycin-mediated apoptosis of leukemia HL-60 cells depends upon JNK1 (24).…”

Section: Fig 7 Anisomycin and Uv Light Mediated Tyr33 Phosphorylatimentioning

confidence: 99%

JNK1 Physically Interacts with WW Domain-containing Oxidoreductase (WOX1) and Inhibits WOX1-mediated Apoptosis

Chang

Doherty²,

Ensign³

2003

Journal of Biological Chemistry

120

358

View full text Add to dashboard Cite

c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for mitoxantrone- and anisomycin-induced apoptosis in HL-60 cells

Cited by 104 publications

References 41 publications

Requirement for SAPK–JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells

Requirement for SAPK–JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells

Opposing Roles of c-Jun NH2-Terminal Kinase and p38 Mitogen-Activated Protein Kinase in the Cellular Response to Ionizing Radiation in Human Cervical Cancer Cells

JNK1 Physically Interacts with WW Domain-containing Oxidoreductase (WOX1) and Inhibits WOX1-mediated Apoptosis

Contact Info

Product

Resources

About