Involvement of Stress Kinase Mitogen-activated Protein Kinase Kinase 7 in Regulation of Mammalian Circadian Clock

Abstract

Background: MKK7 is a kinase involved in the cellular stress response. Results: MKK7 regulates circadian gene expression and the stability of an essential circadian component in unstressed mammalian cells. Conclusion: MKK7 functions as a circadian clock regulator. Significance: Our identification of role of MKK7 in the circadian clock provides insight into the importance of stress-responsive molecules in the maintenance of cellular homeostasis.

Diverse Roles for MAPK Signaling in Circadian Clocks

“…JNK kinase modulates the properties of the circadian oscillator by phosphorylating the clock proteins in both the positive and negative branches of the oscillator (Uchida et al, 2012; Yoshitane et al, 2012) (Figure 1.9). BMAL1 protein, which forms the positive component of the mouse oscillator upon heterodimerization with CLOCK, interacts with JNK in vitro (Uchida et al, 2012).…”

“…JNK kinase modulates the properties of the circadian oscillator by phosphorylating the clock proteins in both the positive and negative branches of the oscillator (Uchida et al, 2012; Yoshitane et al, 2012) (Figure 1.9). BMAL1 protein, which forms the positive component of the mouse oscillator upon heterodimerization with CLOCK, interacts with JNK in vitro (Uchida et al, 2012). The phosphorylation of BMAL1 increases following activation of the JNK pathway and decreases following inhibition of JNK activity in in vitro cell culture (Uchida et al, 2012; Yoshitane et al, 2012).…”

“…BMAL1 protein, which forms the positive component of the mouse oscillator upon heterodimerization with CLOCK, interacts with JNK in vitro (Uchida et al, 2012). The phosphorylation of BMAL1 increases following activation of the JNK pathway and decreases following inhibition of JNK activity in in vitro cell culture (Uchida et al, 2012; Yoshitane et al, 2012). In the negative branch of the circadian oscillator, JNK MAPK interacts with PER2, and its activity increases PER2 phosphorylation (Uchida et al, 2012) (Figure 1.9).…”

The mevalonate pathway regulates primitive streak formation via protein farnesylation

“…RNA isolation and RT-PCR were performed as described elsewhere30. Briefly, ES cells or EBs were collected and immediately suspended in TRI reagent (Molecular Research Centre).…”

“…WB was performed as previously described30, with slight modifications. Proteins were extracted in RIPA buffer, fractionated by SDS/PAGE and transferred to PVDF membranes.…”