Limits...
Mnt-Max to Myc-Max complex switching regulates cell cycle entry.

Walker W, Zhou ZQ, Ota S, Wynshaw-Boris A, Hurlin PJ - J. Cell Biol. (2005)

Bottom Line: Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes.Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry.These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Shriners Hospitals for Children, Portland, OR 97201, USA.

ABSTRACT
The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes. Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry. Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse embryo fibroblasts rescued the cell cycle entry and proliferative block caused by c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.

Show MeSH
Effect of acute Mnt, c-Myc, and Mnt plus c-Myc deletion on the expression levels of proteins involved in the regulation of cell proliferation. Cell extracts were obtained from primary MEFs after AdCre-mediated deletion of Mnt, c-Myc, or both Mnt and c-Myc as shown in Fig. 5 (a and b). Western blots were performed with antibodies against the indicated proteins.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2171929&req=5

fig6: Effect of acute Mnt, c-Myc, and Mnt plus c-Myc deletion on the expression levels of proteins involved in the regulation of cell proliferation. Cell extracts were obtained from primary MEFs after AdCre-mediated deletion of Mnt, c-Myc, or both Mnt and c-Myc as shown in Fig. 5 (a and b). Western blots were performed with antibodies against the indicated proteins.

Mentions: To further characterize how Mnt deletion rescued proliferation arrest caused by loss of c-Myc, a series of Western blots were performed examining the expression of proteins that perform critical functions in cell cycle control (Fig. 6). From this analysis, it was observed that several proteins up-regulated by loss of Mnt, including Cyclin D2, Cyclin A, Cyclin B, Cyclin E, and p107, were also up-regulated in Mnt/c-MycdCKO MEFs, relative to their expression in c-Myc–deficient MEFs (Fig. 6). In addition, pRB was hyperphosphorylated by Mnt deletion, both in the presence and absence of c-Myc. These results suggest that Mnt deletion rescues the proliferation arrest caused by c-Myc deletion at least partly through up-regulation of critical cell cycle regulatory proteins.


Mnt-Max to Myc-Max complex switching regulates cell cycle entry.

Walker W, Zhou ZQ, Ota S, Wynshaw-Boris A, Hurlin PJ - J. Cell Biol. (2005)

Effect of acute Mnt, c-Myc, and Mnt plus c-Myc deletion on the expression levels of proteins involved in the regulation of cell proliferation. Cell extracts were obtained from primary MEFs after AdCre-mediated deletion of Mnt, c-Myc, or both Mnt and c-Myc as shown in Fig. 5 (a and b). Western blots were performed with antibodies against the indicated proteins.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171929&req=5

fig6: Effect of acute Mnt, c-Myc, and Mnt plus c-Myc deletion on the expression levels of proteins involved in the regulation of cell proliferation. Cell extracts were obtained from primary MEFs after AdCre-mediated deletion of Mnt, c-Myc, or both Mnt and c-Myc as shown in Fig. 5 (a and b). Western blots were performed with antibodies against the indicated proteins.
Mentions: To further characterize how Mnt deletion rescued proliferation arrest caused by loss of c-Myc, a series of Western blots were performed examining the expression of proteins that perform critical functions in cell cycle control (Fig. 6). From this analysis, it was observed that several proteins up-regulated by loss of Mnt, including Cyclin D2, Cyclin A, Cyclin B, Cyclin E, and p107, were also up-regulated in Mnt/c-MycdCKO MEFs, relative to their expression in c-Myc–deficient MEFs (Fig. 6). In addition, pRB was hyperphosphorylated by Mnt deletion, both in the presence and absence of c-Myc. These results suggest that Mnt deletion rescues the proliferation arrest caused by c-Myc deletion at least partly through up-regulation of critical cell cycle regulatory proteins.

Bottom Line: Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes.Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry.These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Shriners Hospitals for Children, Portland, OR 97201, USA.

ABSTRACT
The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes. Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry. Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse embryo fibroblasts rescued the cell cycle entry and proliferative block caused by c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.

Show MeSH