Two Distinct Mechanisms Control the Accumulation of Cyclin B1 and Mos inXenopusOocytes in Response to Progesterone

Abstract

Progesterone-induced meiotic maturation of Xenopus oocytes requires the synthesis of new proteins, such as Mos and cyclin B. Synthesis of Mos is thought to be necessary and sufficient for meiotic maturation; however, it has recently been proposed that newly synthesized proteins binding to p34 cdc2 could be involved in a signaling pathway that triggers the activation of maturation-promoting factor. We focused our attention on cyclin B proteins because they are synthesized in response to progesterone, they bind to p34 cdc2 , and their microinjection into resting oocytes induces meiotic maturation. We investigated cyclin B accumulation in response to progesterone in the absence of maturation-promoting factor-induced feedback. We report here that the cdk inhibitor p21 cip1 , when microinjected into immature Xenopus oocytes, blocks germinal vesicle breakdown induced by progesterone, by maturation-promoting factor transfer, or by injection of okadaic acid. After microinjection of p21 cip1 , progesterone fails to induce the activation of MAPK or p34 cdc2 , and Mos does not accumulate. In contrast, the level of cyclin B1 increases normally in a manner dependent on down-regulation of cAMP-dependent protein kinase but independent of cap-ribose methylation of mRNA.

Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation independently of Mos and p42MAPK

“…In the absence of active cdc2, Cyclin B1 was accumulated in response to progesterone, but Mos accumulation was prevented and both p42 MAPK and RSK remained inactive ( Figure 6). Therefore, as previously reported (Frank-Vaillant et al, 1999), cdc2 activity induced by progesterone controls the Mos/ p42 MAPK pathway. Similarly, Cyclin B1 was accumulated in response to Xe H-RasV12 injection even when cdc2 activation was blocked by p21 cip1 (Figure 6a).…”

“…Surprisingly, progesterone can lead to cdc2 activation and GVBD in the absence of p42 MAPK activation (Fisher et al, 1999;Gross et al, 2000). Moreover, the use of the Cdk inhibitor, p21 cip1 , demonstrated that cdc2 activation is required for Mos accumulation, and consequently for p42 MAPK activation (Frank-Vaillant et al, 1999). Therefore, although ectopic expression of Mos and p42 MAPK is able to lead to cdc2 activation, the physiological requirement of the Mos/p42 MAPK pathway for cdc2 activation remains questionable.…”

“…To directly ascertain that cdc2 activation is not required for p42 MAPK activation induced by Xe HRasV12, we used the CDK inhibitor p21 cip1 , which specifically binds cdc2 in ovo and prevents its activation in response to progesterone (Frank-Vaillant et al, 1999). p21 cip1 was injected into prophase oocytes.…”

“…The oocyte completes the first meiotic division and then arrests again in metaphase of the second meiotic cell division (Metaphase II), a process known as meiotic maturation (for review, see Karaiskou et al, 2001). Progesterone addition induces a drop in cAMP concentration, leading to the inhibition of the cAMPdependent protein kinase (PKA) activity, and subsequently to the synthesis of new proteins, among them Cyclin B1/B4 and the serine/threonine kinase Mos, product of the c-mos proto-oncogene (Frank-Vaillant et al, 1999;Hochegger et al, 2001;Matten et al, 1994;Sagata et al, 1988). Mos accumulates at the time of germinal vesicle breakdown (GVBD), leading indirectly to p42 MAPK activation, which ultimately phosphorylates RSK (Ribosomal S6 Kinase) (Karaiskou et al, 2001).…”

Cdc2 and Mos Regulate Emi2 Stability to Promote the Meiosis I–Meiosis II Transition

“…MI entry is driven by the Cdc2/cyclin B kinase, the molecular components of an activity known as maturation promoting factor (MPF; Masui, 2001;Doree and Hunt, 2002;Jones, 2004). In the well-characterized Xenopus oocyte system, progesterone treatment initiates the translation of several proteins that trigger maturation, including cyclin B and the Mos kinase (Frank-Vaillant et al, 1999). Mos facilitates MI entry through activation of the ERK-MAPK pathway, which promotes Cdc2 activation by antagonizing its inhibitory kinase, Myt1, and by enhancing the activity of its activating phosphatase, Cdc25 (Sagata et al, 1988;Palmer et al, 1998;Peter et al, 2002).…”