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- Bengoechea-Alonso, Maria T., et al.
(författare)
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Cdk1/cyclin B-mediated phosphorylation stabilizes SREBP1 during mitosis
- 2006
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Ingår i: Cell Cycle. - 1538-4101 .- 1551-4005. ; 5:15, s. 1708-1718
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Tidskriftsartikel (refereegranskat)abstract
- Members of the sterol regulatory element-binding protein (SREBP) family of transcription factors control the biosynthesis of cholesterol and other lipids, and lipid synthesis is critical for cell growth and proliferation. We recently found that the mature forms of SREBP1a and SREBP1c are hyperphosphorylated in mitotic cells, giving rise to a phosphoepitope recognized by the mitotic protein monoclonal-2 (MPM-2) antibody. In addition, we found that mature SREBP1 was stabilized in a phosphorylation-dependent manner during mitosis. We have now mapped the major MPM-2 epitope to a serine residue, S439, in the C terminus of mature SREBP1. Using phosphorylation-specific antibodies, we demonstrate that endogenous SREBP1 is phosphorylated on S439 specifically during mitosis. Mature SREBP1 interacts with the Cdk1/cyclin B complex in mitotic cells and we demonstrate that Cdk1 phosphorylates S439, both in vitro and in vivo. Our results suggest that Cdk1-mediated phosphorylation of S439 stabilizes mature SREBP1 during mitosis, thereby preserving a critical pool of active transcription factors to support lipid synthesis. Taken together with our previous work, the current study suggests that SREBP1 may provide a link between lipid synthesis, proliferation and cell growth. This hypothesis was supported by our observation that siRNA-mediated inactivation of SREBP1 arrested cells in the G(1) phase of the cell cycle, thereby attenuating cell growth.
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- Bergström, Rosita, et al.
(författare)
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CTCF Regulates Asynchronous Replication of the Imprinted H19/Igf2 Domain
- 2007
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Ingår i: Cell Cycle. - : Informa UK Limited. - 1538-4101 .- 1551-4005. ; 6:4, s. 450-454
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Tidskriftsartikel (refereegranskat)abstract
- Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/lgf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/ lgf2 domain.
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- Bernander, Rolf, et al.
(författare)
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Comparative and functional analysis of the archaeal cell cycle
- 2010
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Ingår i: Cell Cycle. - : Informa UK Limited. - 1538-4101 .- 1551-4005. ; 9:4, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- The temporal and spatial organization of the chromosome replication, genome segregation and cell division processes is less well understood in species belonging to the Archaea, than in those from the Bacteria and Eukarya domains. Novel insights into the regulation and key components of the Sulfolobus acidocaldarius cell cycle have been obtained through genome-wide analysis of cell cycle-specific gene expression, followed by cloning and characterization of gene products expressed at different cell cycle stages. Here, the results of the transcript profiling are further explored, and potential key players in archaeal cell cycle progression are highlighted in an evolutionary context, by comparing gene expression patterns and gene conservation between three selected microbial species from different domains of life. We draw attention to novel putative nucleases and helicases implicated in DNA replication, recombination and repair, as well as to potential genome segregation factors. Focus is also placed upon regulatory features, including transcription factors and protein kinases inferred to be involved in the execution of specific cell cycle stages, and regulation through metabolic coupling is discussed.
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