|
General Comment |
NCBI Summary:
Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]
|
|
Comment |
Apoptosis signal-regulating kinase (ASK-1) controls ovarian cell functions. Sirotkin AV et al. (2020) The involvement of the apoptosis signal-regulating kinase 1 (ASK1)-related signalling pathway in the control of reproduction is unknown. This study aimed to investigate the role of ASK-1 in the control of basic ovarian functions (proliferation, apoptosis and hormone release) and its response to ovarian hormonal regulators (leptin and FSH). We compared the accumulation of ASK-1, proliferation marker proliferating cell nuclear antigen (PCNA), apoptosis marker Bax and apoptosis and proliferation regulating transcription factor p53 and the release of progesterone (P4), oxytocin (OT), insulin-like growth factor I (IGF-I) and prostaglandins F (PGF) and E (PGE) using cultured porcine ovarian granulosa cells transfected with ASK-1 cDNA and cultured with leptin or FSH. This study is the first to demonstrate that ASK-1 does not affect cell apoptosis and viability in ovarian cells, but promotes cell proliferation, suppresses p53, alters the release of ovarian hormones (P4, OT, IGF-I, PGF and PGE) and defines their response to the upstream hormonal regulators leptin and FSH. Therefore, ASK-1 can be considered a new and important regulator of multiple ovarian functions.////////////////// Apoptosis signal-regulating kinase (ASK-1) controls ovarian cell functions. Sirotkin AV et al. (2019) The involvement of the apoptosis signal-regulating kinase 1 (ASK1)-related signalling pathway in the control of reproduction is unknown. This study aimed to investigate the role of ASK-1 in the control of basic ovarian functions (proliferation, apoptosis and hormone release) and its response to ovarian hormonal regulators (leptin and FSH). We compared the accumulation of ASK-1, proliferation marker proliferating cell nuclear antigen (PCNA), apoptosis marker Bax and apoptosis and proliferation regulating transcription factor p53 and the release of progesterone (P4), oxytocin (OT), insulin-like growth factor I (IGF-I) and prostaglandins F (PGF) and E (PGE) using cultured porcine ovarian granulosa cells transfected with ASK-1 cDNA and cultured with leptin or FSH. This study is the first to demonstrate that ASK-1 does not affect cell apoptosis and viability in ovarian cells, but promotes cell proliferation, suppresses p53, alters the release of ovarian hormones (P4, OT, IGF-I, PGF and PGE) and defines their response to the upstream hormonal regulators leptin and FSH. Therefore, ASK-1 can be considered a new and important regulator of multiple ovarian functions.//////////////////
Apoptosis signal-regulating kinase (ASK1) and transcription factor tumor suppressor protein TP53 suppress rabbit ovarian granulosa cell functions. Sirotkin AV et al. (2019) This study was conducted with the aim to understand the roles of apoptosis signal-regulating kinase (ASK1) and transcription factor tumor suppressor protein TP53, as well as the possible interrelationships, in the control of healthy ovarian cell functions. Rabbit ovarian granulosa cells were transfected with constructs encoding ASK1, TP53, or TP53 + ASK1 and cultured with or without insulin-like growth factor 1 (IGF1). The accumulation of ASK1, the cytoplasmic apoptosis regulators BAX and BCL2, and proliferating cell nuclear antigen (PCNA, a cell proliferation marker), as well as progesterone release, were evaluated by quantitative immunocytochemistry and radioimmunoassay. Results indicate both ASK1 and TP53 promoted the accumulation of BAX, but suppressed that of BCL2 and PCNA. Progesterone release was inhibited by ASK1 and promoted by TP53, while TP53 also stimulated ASK1 accumulation. Additionally, IGF1 stimulated PCNA and reduced progesterone release, but did not affect ASK1. Transfection with ASK1, TP53, or TP53 + ASK1 could modify IGF1 activity, however, there was no cumulative effect with co-transfection of TP53 and ASK1. This is the first results that indicate there is ASK1 suppression of healthy ovarian granulosa cell functions, including promoting apoptosis, inhibiting proliferation, and alter progesterone release. There was also TP53 actions in rabbit ovarian granulosa cells, where it stimulated ASK1, apoptosis, and progesterone release, thus suppressing proliferation and responses to IGF1. The similarity of ASK1 and TP53 effects on apoptosis and proliferation, lack of cumulative action of these molecules, and capacity of TP53 to promote ASK1 accumulation suggest that TP53 can suppress some ovarian granulosa cell functions through ASK1 stimulation.//////////////////
Sisco B, et al 2003 reported the isolation of genes differentially expressed in dominant and subordinate bovine follicles.
In monoovulatory species such as cattle, unknown mechanisms lead to the selection of one of a cohort of developing ovarian follicles to assume dominance and continue to grow in each follicular wave. The authors have used suppressive subtraction hybridization to identify genes differentially expressed in the granulosa cells of dominant and subordinate follicles. Inhibin betaA, apolipoprotein E receptor 2, MAPKkinase kinase 5 (ask1), and carboxypeptidase D were isolated and verified to be reliable markers for dominant follicles using real-time RT-PCR. Before the time point at which dominant follicles can be distinguished by virtue of their deviation in size and growth rate, transcripts for inhibin betaA, apolipoprotein E receptor 2, and p450 aromatase were elevated specifically in the one to three largest follicles. On d 2.5 postovulation, near the time of dominant follicle selection, the mRNA expression profiles of MAPK kinase kinase 5 and carboxypeptidase D paralleled those of the other three genes, thus anticipating the clear molecular expression differences seen between the dominant follicle and the next largest follicle 1 d later.
|
|
Comment |
Estrogen inhibits paclitaxel-induced apoptosis via the phosphorylation of apoptosis signal-regulating kinase 1 in human ovarian cancer cell lines
Mabuchi S,et al .
The influence of postoperative estrogen replacement therapy on the sensitivity of ovarian cancer to paclitaxel remains elusive. We examined whether estrogen affects paclitaxel-induced apoptosis in the Caov-3 human ovarian cancer cell line, which expresses estrogen receptor. 17beta-Estradiol (E2) significantly reversed the paclitaxel-induced apoptosis and reduction of cell viability, and a highly selective estrogen receptor antagonist, ICI182,780, and a phosphatidylinositol 3-kinase inhibitor, LY294002, attenuated the reversal effect of E2 on paclitaxel-induced apoptosis and reduction of cell viability. E2 significantly induced the phosphorylation of Akt. Akt and apoptosis signal-regulating kinase 1 (ASK1) were physically associated, and E2 induced the phosphorylation of ASK1 at serine-83, which is a consensus Akt phosphorylation site. We confirmed a previous report showing that paclitaxel induces cell damage via the ASK1-c-Jun N-terminal protein kinase (JNK) cascade. E2 inhibited the paclitaxel-induced JNK activation, and the E2-induced inhibition of the paclitaxel-induced JNK activation was attenuated in cells treated with either ICI182,780 or LY294002 or transfected with ASK1S83A, in which a consensus Akt phosphorylation site at serine-83 was converted to alanine. The inhibitory effect of E2 on the paclitaxel-induced reduction of cell viability and apoptosis was diminished in cells transfected with ASK1S83A. These results indicate that E2 inhibits paclitaxel-induced cell damage by inhibiting JNK activity via phosphorylation of Akt-ASK1. Thus, treatment of ovarian cancer with paclitaxel might be less effective in the setting of postoperative estrogen replacement therapy.
|