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M Oskarsson

Publications and source records attributed to M Oskarsson.

11 recordsLinked to original sources
PubMed1991

Ability of the c-mos product to associate with and phosphorylate tubulin.

The mos proto-oncogene product, pp39mos, is a protein kinase and has been equated with cytostatic factor (CSF), an activity in unfertilized eggs that is thought to be responsible for the arrest of meiosis at metaphase II. The biochemical properties and potential substrates of pp39mos were examined in unfertilized eggs and in transformed cells in order to study how the protein functions both as CSF and in transformation. The pp39mos protein associated with polymers under conditions that favor tubulin oligomerization and was present in an approximately 500-kilodalton "core" complex under conditions that favor depolymerization. beta-Tubulin was preferentially coprecipitated in pp39mos immunoprecipitates and was the major phosphorylated product in a pp39mos-dependent immune complex kinase assay. Immunofluorescence analysis of NIH 3T3 cells transformed with Xenopus c-mos showed that pp39mos colocalizes with tubulin in the spindle during metaphase and in the midbody and asters during telophase. Disruption of microtubules with nocodazole affected tubulin and pp39mos organization in the same way. It therefore appears that pp39mos is a tubulin-associated protein kinase and may thus participate in the modification of microtubules and contribute to the formation of the spindle. This activity expressed during interphase in somatic cells may be responsible for the transforming activity of pp39mos.

Amino Acid Sequence↗
PubMed1991

mos gene transforming efficiencies correlate with oocyte maturation and cytostatic factor activities.

The mos proto-oncogenes from different vertebrate species transform mouse NIH 3T3 cells with markedly different efficiencies. v-mos, mouse (c-mosmu), and chicken (c-mosch) mos transform NIH 3T3 cells 10- to 100-fold more efficiently than do human (c-moshu) and Xenopus (c-mosxc) mos. The mos genes with the highest transforming activity efficiently induce maturation in Xenopus oocytes and mimic cytostatic factor (CSF) by causing mitotic cleavage arrest in embryos. Chimeric v-mos/c-moshu proteins that had high transforming efficiencies in NIH 3T3 cells were also effective in the induction of oocyte maturation and CSF cleavage arrest. We measured the in vitro autophosphorylation activities of the different mos proteins and found that the levels of kinase activity of v-mos, c-mosmu, and c-mosch were much higher than that of c-mosxc. These data indicate that mos gene transforming efficiency and the ability to induce oocyte maturation or mimic CSF activity are correlated with in vitro autophosphorylation activity and suggest that the mos protein plays a similar role in transformed cells and normal oocytes.

Animals↗
PubMed1990

mos proto-oncogene function.

Maturation promoting factor (MPF) is a cytoplasmic activity that causes oocytes arrested in prophase to resume meiosis. An inactive form of MPF termed pre-MPF exists in fully grown oocytes. In Xenopus oocytes, progesterone induces maturation and pre-MPF activation. These early maturation events require protein synthesis. We have shown that p39mos synthesis is rapidly induced in progesterone-treated Xenopus oocytes during the protein synthesis sensitive period and prior to activation of pre-MPF or germinal vesicle breakdown (GVBD). p39mos may qualify, therefore, as an 'initiator' of maturation. Mouse oocytes undergoing meiotic maturation also express p39mos. Microinjection of antisense mos oligodeoxynucleotides into fully grown mouse and Xenopus oocytes results in the block of meiotic maturation. In Xenopus, antisense-injected oocytes not only lack p39mos, but also lack MPF and fail to undergo GVBD. In the mouse, the microinjected oocytes progress through GVBD, but fail to produce the first polar body; cytogenetic analysis shows they are arrested at the bivalent chromosome stage of metaphase I. This and additional studies with Xenopus oocytes indicate that p39mos is also required throughout maturation. We have shown that p39mos is indistinguishable from the protein product constitutively expressed in NIH/3T3 cells transformed with activated c-mos. It is likely that its activity as a transforming gene may be due to activation of pre-MPF activities in interphase in the somatic cell cycle.

Animals↗
PubMed1990

An oncogenic chromosome 8-9 gene fusion isolated following transfection of human ovarian carcinoma cell line DNA.

Transfection of NIH3T3 cells with genomic DNA from the human ovarian adenocarcinoma tumor cell line OVCAR-3 identified ovc, a rearranged human DNA sequence which was generated during transfection and which induced both morphological transformation and tumorigenesis. A human alu repeat positive 10.5 kb EcoRI fragment present in all transformants was cloned, and two alu-free fragments of 1.8 kb and 2.2 kb were subcloned. The cloned 10.5 kb fragment is not biologically active in DNA transfection assays. Probe from the 2.2 kb fragment hybridizes to poly A + RNA from the transformants and several human tumor cell lines, including OVCAR-3. The 2.2 kb fragment maps to a site on human chromosome 9 (9p24) not known to contain oncogenic sequences, and identifies a two allele polymorphic restriction site. The 1.8 kb fragment maps to human chromosome 8. The ovc transforming sequences fail to hybridize to probes to any of 14 known oncogenes, indicating that they may represent a previously unknown human transforming gene.

Blotting, Northern↗
PubMed1989

The product of the mos proto-oncogene as a candidate "initiator" for oocyte maturation.

The endogenous c-mos product, pp39mos, is required for progesterone-induced meiotic maturation in Xenopus oocytes. Treatment of oocytes with progesterone induced a rapid increase in pp39mos that preceded both the activation of maturation promoting factor (MPF) and germinal vesicle breakdown (GVBD). Microinjection of synthetic mos RNA into oocytes activated MPF and induced GVBD in the absence of progesterone. Thus, the mos proto-oncogene product may qualify as a candidate "initiator" protein of MPF and is at least one of the "triggers" for G2 to M transition.

Animals↗
PubMed1988

Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes.

The c-mos proto-oncogene is expressed as a maternal mRNA in oocytes and early embryos of Xenopus laevis, but its translation product pp39mos is detectable only during progesterone-induced oocyte maturation. Microinjection of mos-specific antisense oligonucleotides into oocytes not only prevents expression of pp39mos, but also blocks germinal vesicle breakdown, indicating that it functions during reinitiation of meiotic division.

Animals↗
PubMed1986

Mechanism of activation of human ras genes cloned from a gastric adenocarcinoma and a pancreatic carcinoma cell line.

We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be rearranged or amplified. A molecular clone, which contained an EcoRI fragment spanning the first and second rasN exons, was molecularly cloned directly from the human tumor DNA. Chimeric constructions and DNA sequencing defined the mechanism of activation of the gene as a mutation in the 61st amino acid codon substituting arginine for glutamine. Normal DNA isolated from Epstein-Barr virus immortalized lymphocytes derived from the same patient did not induce morphological transformation or tumorigenicity in NIH3T3 cells. A cloned cell line isolated from the human pancreatic carcinoma cell line Panc1 had previously been shown to contain an activated rasK-2. Sequence analysis of the cloned transfected gene reveals a G to A change within codon 12, which is presumably responsible for its biological activity. This represents the first identification of a codon 12 aspartic acid substitution of a c-rask oncogene from a human tumor-derived cell line.

Adenocarcinoma↗
PubMed1979

Cloning of integrated Moloney sarcoma proviral DNA sequences in bacteriophage lambda.

We have identified integrated proviral DNA sequences of m1 and HT-1 isolates of Moloney sarcoma virus (MuSV) in EcoRI digests of transformed mink cell genomic DNA and have cloned these fragments in bacteriophage lambda. Both the lambda-HT1 phage recombinant, containing a 12.3-kilobase MuSV pair (kb) fragment, and the lambda-m1 phage recombinant, containing a 7.0-kb fragment, possess full copies of the sarcoma viruses along with 5' and 3' host flanking sequences. The MuSV proviral DNA sequences, 6.7 kb for HT-1 and 5.2 kb for m1, are colinear by heteroduplex microscopy with the 1.5-kb difference in size accounted for by two approximately equal to 0.8-kb deleted regions in m1. Both integrated viral genomes are terminally redundant and have integrated at the same site in the provirus but at different sites on the host chromosome. The host sequence flanking integrated HT-1 MuSV have been identified as a single EcoRI restriction fragment of 5.6 kb in normal mink cells.

Animals↗