Ability of the c- mos Product to Associate with and Phosphorylate Tubulin

Abstract

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.

Mitogen-activated protein kinase pathway is dispensable for microtubule-active drug-induced Raf-1/Bcl-2 phosphorylation and apoptosis in leukemia cells

“…56,57 Microtubules are associated with serine/threonine kinases and phosphatases. [58][59][60][61] As the plasma membrane is an important source of signals during interphase, microtubules may be a principal location of signaling following mitotic arrest. Since mitochondria, an organelle where many members of the Bcl-2 family reside, 62 has proximity to microtubules, this may direct microtubule disruption to the apoptotic machinery.…”

MOS, aneuploidy and the ploidy cycle of cancer cells

“…Here, Mos binds to tubulin and has a role in the bipolar meiotic spindle formation (Zhou et al, 1991;Yew et al, 1993;Verlhac et al, 1996). At early meiosis I, Mos induces nucleation of multiple centrosomes in the vicinity of condensing bivalents.…”

Identification of a Spindlin homolog in gibel carp (Carassius auratus gibelio)

“…In this study, we further demonstrate from the GST pull-down assay that CagSpin directly or indirectly associates with h-tubulin, and therefore provide the first biochemical evidence for the specific interaction of Spindlin protein and h-tubulin, the microtubule component. Interestingly, some important proteins that play crucial functions during oocyte maturation and egg fertilization, such as p39 mos (Zhou et al, 1992;Haccard et al, 1993;Verlhac et al, 1996), p34 cdc2 of metaphase promoting factor (MPF) (Langan et al, 1989;Peter et al, 1990;Verde et al, 1990;Zhou et al, 1991Zhou et al, , 1992, cyclin B, the regulatory component of MPF (Pines and Hunter, 1991;Ookata et al, 1993), MAP kinase (Verlhac et al, 1993) and PKC (Page Baluch et al, 2004), have been also confirmed to associate with microtubules. Interestingly, three putative PKC phosphorylation sites have been revealed in the CagSpin sequence (Fig.…”