Suzumori N et al 2003 reported that RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome
degradation pathway.
Oocyte meiosis and early mitotic divisions in developing embryos rely on the timely
production of cell cycle regulators and their clearance via proteasomal degradation.
Ret Finger Protein-Like 4 (Rfpl4), encoding a RING finger-like protein with a B30.2
domain, was discovered during an in silico search for germ cell-specific genes. To
study the expression and functions of RFPL4 protein, the authors performed
immunolocalizations and used yeast two-hybrid and other protein-protein interaction
assays. Immunohistochemistry and immunofluorescence showed that RFPL4
accumulates in all growing oocytes and quickly disappears during early embryonic
cleavage. The authors used a yeast two-hybrid model to demonstrate that RFPL4 interacts
with the E2 ubiquitin-conjugating enzyme HR6A, proteasome subunit beta type 1,
ubiquitin B, as well as a degradation target protein, cyclin B1.
Coimmunoprecipitation analyses of in vitro translated proteins and extracts of
transiently cotransfected Chinese hamster ovary (CHO)-K1 cells confirmed these
findings. Like many RING-finger containing proteins, RFPL4 is an
E3 ubiquitin ligase. The specificity of its expression and these interactions suggest
that RFPL4 targets cyclin B1 for proteasomal degradation, a key aspect of oocyte cell
cycle control during meiosis and the crucial oocyte-to-embryo transition to mitosis.
General function
Cell proliferation
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Cellular localization
Nuclear
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Ovarian function
Oogenesis
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Expression regulated by
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Ovarian localization
Oocyte
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Genomewide discovery and classification of candidate ovarian fertility genes in the mouse. Gallardo TD et al. Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility. This is an oocyte-specific gene.