Biomedical subjects

A Kokubu

Publications and source records attributed to A Kokubu.

13 recordsLinked to original sources

PubMed2001

ASK1-signaling promotes c-Myc protein stability during apoptosis.

We previously reported that JNK is involved in the regulation of c-Myc-mediated apoptosis triggered by UV irradiation and anticancer drug treatment. Here we show that ASK1 is an upstream regulator for c-Myc-mediated apoptosis triggered by UV, and we found a direct role for Ser-62 and Ser-71 in the regulation of protein stability and function of c-Myc. The ASK1-JNK pathway enhanced the protein stability of c-Myc through phosphorylation at Ser-62 and Ser-71, which was required for c-Myc-dependent apoptosis by ASK1-signaling. Interestingly, ASK1-signaling attenuated the degradation of ubiquitinated c-Myc without affecting the ubiquitination process. Together, these findings indicate that the ASK1-JNK pathway promotes the proapoptotic activity of c-Myc by modulating c-Myc protein stability through phosphorylation at Ser-62 and Ser-71.

3T3 Cells↗

PubMed2000

Differential role of the JNK and p38 MAPK pathway in c-Myc- and s-Myc-mediated apoptosis.

The s-Myc is similar to c-Myc in its ability to induce apoptosis requiring caspase activation. However, s-Myc is distinct from c-Myc in that it has activity to suppress tumor growth and does not require wild-type p53 to induce apoptosis. These facts suggest differential regulation between s-Myc and c-Myc. Here we showed that s-Myc-mediated apoptosis triggered by UV was not inhibited by the inactive form mutant JNK (APF), though c-Myc-mediated apoptosis was. Moreover, we found that JNK did not affect the transactivation activity of s-Myc, but stimulated that of c-Myc. In contrast, both Myc-mediated apoptosis and caspase-3-like protease activation were suppressed by kinase-negative MKK6 and an inactive form mutant p38(AGF). Our results indicate that s-Myc does not require the JNK signaling unlike c-Myc during UV-triggered apoptosis, but the MKK6/p38MAPK pathway might regulate common apoptotic machinery for both s-Myc and c-Myc upstream of caspase.

Animals↗

PubMed2000

[Comparison of the families of terminal stage cancer patients who underwent HPN and the nurses who cared those patients in their thoughts on home care].

In the home care for terminal stage cancer patients, the quality of life of patients has been regarded as more important than the QOL of their family. Now, however, we think the QOL of the family of the patients is as important as that of the patients themselves. We investigated the opinion of the families and nurses by questionnaire in the HPN care for terminal stage cancer patients and compared them. The family answered positively about HPN, but they had a negative opinion in that they do not want to undergo HPN because they felt a heavy burden and responsibility in caring for patients, and they do not want to cause these feelings in others in their family. The nurses also answered positively about HPN, and they answered that they want to undergo HPN if they have terminal stage cancer. These results suggest that the family feels a greater burden and responsibility in caring for patients at home than the medical staff realize. The medical staff should support the family as well as terminal stage cancer patients and should not force our own opinions as medical staff.

Family↗

PubMed2000

[How the lifestyle of families who care for home parenteral nutrition patients changes].

The role of families who care for home parenteral nutrition (HPN) patients is extremely important. They face many problems not only in caring for patients but also in their own lifestyle. We investigated by questionnaire the changes in the family of terminal stage cancer patients receiving HPN. Replies submitted to the questionnaire were obtained from 20 out of 32 families who underwent HPN in the Osaka Prefectural General Hospital. Ten out of 20 people answered that they changed their lifestyle during HPN. The changes were decreased opportunity to communicate with other people and decreased time for to spend on a hobby or other activity. The care of the HPN patients affects the wife, daughter-in-law and children more than the husband of the patient, because the former have to manage housekeeping as well as patient care. This result suggests that the quality of life of the family of terminal stage cancer patients at home with HPN declined because they had to change their own lifestyle in order to spare time to care for the patients.

Family↗

PubMed1999

Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase.

The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c-Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)-dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc-expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser-71.

3T3 Cells↗

PubMed1986