Intronless Pabpc6 encodes a testis-specific, cytoplasmic poly(A)-binding protein but is dispensable for spermatogenesis in the mouse†.

Besides ubiquitous poly(A)-binding protein, cytoplasmic 1 (PABPC1), testis-specific PABPC2/PABPt (in humans, referred to as PABPC3), and female and male germline-specific PABPC1L/ePAB, have been reported in the mouse testis. Recent in silico analysis additionally identified testis-specific Pabpc6 in the mouse. In this study, we characterized PABPC6 and its mutant mice.

Biogenesis of sperm acrosome is regulated by pre-mRNA alternative splicing of Acrbp in the mouse.

Proper biogenesis of a sperm-specific organelle, the acrosome, is essential for gamete interaction. An acrosomal matrix protein, ACRBP, is known as a proacrosin-binding protein. In mice, two forms of ACRBP, wild-type ACRBP-W and variant ACRBP-V5, are generated by pre-mRNA alternative splicing of Acrbp Here, we demonstrate the functional roles of these two ACRBP proteins.

SCFFbl12 Increases p21Waf1/Cip1 Expression Level through Atypical Ubiquitin Chain Synthesis.

The cyclin-dependent kinase (CDK) inhibitor p21 is an unstructured protein regulated by multiple turnover pathways. p21 abundance is tightly regulated, and its defect causes tumor development. However, the mechanisms that underlie the control of p21 level are not fully understood.

Surfing and Swimming of Ejaculated Sperm in the Mouse Oviduct.

To accomplish fertilization in the oviductal ampulla, ejaculated sperm are required to migrate through the female reproductive tract. However, this fundamental process largely remains unknown. In this study, we focused on the role of oviductal smooth muscle (myosalpinx) contractions in the sperm migration.

Possible role of p38 MAPK-MNK1-EMI2 cascade in metaphase-II arrest of mouse oocytes.

The Mos-MAPK signaling pathway involving the Mos-MEK1/2-ERK1/2-RSK1/2/3 or MSK1-EMI2 cascade is directly linked to metaphase-II arrest of vertebrate oocytes. In this study, we examined whether p38, a member of the MAPK subfamily, is regulated under the control of Mos and contributes to metaphase-II arrest in the mouse oocyte. Morpholino oligonucleotide-mediated depletion of Mos revealed a remarkable decrease in phosphorylation of p38.

Two functional forms of ACRBP/sp32 are produced by pre-mRNA alternative splicing in the mouse.

ACRBP/sp32 is a binding protein specific for the precursor (pro-ACR) and intermediate forms of sperm serine protease ACR. In this study, we examined the expression pattern, localization, and possible role of mouse ACRBP in spermatogenic cells and epididymal sperm. Unlike other mammalian ACRBPs, two forms of Acrbp mRNA-wild-type Acrbp-W and variant Acrbp-V5 mRNAs-were generated by alternative splicing of Acrbp in the mouse.

Possible involvement of mitogen- and stress-activated protein kinase 1, MSK1, in metaphase-II arrest through phosphorylation of EMI2 in mouse oocytes.

Ovulated oocytes are arrested at the metaphase of second meiotic division. The metaphase-II arrest in Xenopus oocytes is regulated by RSKs located downstream of the Mos-MAPK pathway. In mice, other kinase(s) besides RSKs may be responsible for the metaphase-II arrest, because RSK1/RSK2/RSK3-triple knockout mice exhibit no obvious phenotype.

Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic arrest of Xenopus eggs.

In vertebrates, unfertilized eggs are arrested at metaphase of meiosis II by Mos and Emi2, an inhibitor of the APC/C ubiquitin ligase. In Xenopus, Cdk1 phosphorylates Emi2 and both destabilizes and inactivates it, whereas Mos recruits PP2A phosphatase to antagonize the Cdk1 phosphorylation. However, how Cdk1 phosphorylation inhibits Emi2 is largely unknown.

Emi2 inhibition of the anaphase-promoting complex/cyclosome absolutely requires Emi2 binding via the C-terminal RL tail.

Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C.

The extracellular signal-regulated kinase-mitogen-activated protein kinase pathway phosphorylates and targets Cdc25A for SCF beta-TrCP-dependent degradation for cell cycle arrest.

The extracellular signal-regulated kinase (ERK) pathway is generally mitogenic, but, upon strong activation, it causes cell cycle arrest by a not-yet fully understood mechanism. In response to genotoxic stress, Chk1 hyperphosphorylates Cdc25A, a positive cell cycle regulator, and targets it for Skp1/Cullin1/F-box protein (SCF)(beta-TrCP) ubiquitin ligase-dependent degradation, thereby leading to cell cycle arrest. Here, we show that strong ERK activation can also phosphorylate and target Cdc25A for SCF(beta-TrCP)-dependent degradation.

A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs.

In vertebrates, unfertilized eggs (or mature oocytes) are arrested at metaphase of meiosis II by a cytoplasmic activity called cytostatic factor (CSF). The classical Mos-MAPK pathway has long been implicated in CSF arrest of vertebrate eggs, but exactly how it exerts CSF activity remains unclear. Recently, Erp1 (also called Emi2), an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) required for degradation of the mitotic regulator cyclin B (ref.

Erp1/Emi2 is essential for the meiosis I to meiosis II transition in Xenopus oocytes.

Erp1 (also called Emi2), an inhibitor of the APC/C ubiquitin ligase, is a key component of cytostatic factor (CSF) responsible for Meta-II arrest in vertebrate eggs. Reportedly, however, Erp1 is expressed even during meiosis I in Xenopus oocytes. If so, it is a puzzle why normally maturing oocytes cannot arrest at Meta-I.

Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases.

Beta-TrCP, the F-box protein of the SCF(beta-TrCP) ubiquitin ligase (SCF, Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif (DpSGPhiXpS) in various SCF(beta-TrCP) target proteins. The Cdc25A phosphatase, a key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin-dependent degradation in response to genotoxic stress. Beta-TrCP binds to the DSG motif of human Cdc25A in a manner dependent on Chk1 and other unknown kinases.