Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.

Dong, Xinzhong; Zavitz, Kenton H.; Thomas, Barbara J.; Lin, Michael; Campbell, Shelagh D.; Zipursky, S. Lawrence

doi:10.1101/gad.11.1.94

Cited by 101 publications

(81 citation statements)

References 56 publications

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“…In contrast, the polyploidization of megakaryocytes results in the multiplication and segregation of normally duplicated chromosomes. Complete S and G2 phases should then be maintained, and this could explain the need for cyclin A expression, the role of which in the progression of S into G2 phase has been suggested not only in mammalian cells (Pagano et al, 1992;Pines, 1993), but also in the Drosophila embryo and developing eye (Dong et al, 1997;Sprenger et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

et al. 2000

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Megakaryocytes become polyploid by entering a truncated cell cycle, consisting of alternate S phases and abortive mitoses. We have investigated the regulation of the G1/S transition by comparing two megakaryoblastic cell lines, HEL and K562, which respectively do or do not become polyploid in response to phorbol esters. A pronounced downregulation of cyclin A, and to a lesser extent of cyclin E, occurred in K562 cells during the ®rst 24 h after TPA treatment, in contrast with re-replicating HEL cells, in which both cyclins were present in individual G2/M cells. Transactivation experiments suggested that the absence of cyclin A in di erentiated K562 cells could be due to a TPA-mediated inhibition of its transcription. To investigate the potential role of cyclin E in the establishment of re-replication cycles, we isolated K562 clones constitutively expressing cyclin E. The resulting clones, and also K562 cells transiently expressing cyclin E, entered re-replication cycles when treated with TPA. The transcriptional activity of the cyclin A promoter was not inhibited after TPA treatment, and although the levels of cyclin A¯uctuated during further re-replication cycles, they never decreased below S phase levels. We conclude that the presence of cyclin E in megakaryoblastic G2/M cells determines cyclin A expression and allows the entrance into an extra S phase.

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Section: Discussionmentioning

confidence: 99%

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

et al. 2000

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“…As a consequence of cell cycle defects, photoreceptor differentiation and pattern formation in the eye are disrupted. Whereas cell cycle regulators enhance and suppress the primary cell cycle phenotype (Thomas et al 1994;Dong et al 1997;K.H. Zavitz and S.L.…”

Section: Loss-of-function Mutations In Ebi and Egfr Have Similar Phenmentioning

confidence: 99%

“…ebi mutations were identified in a screen for enhancers of an eye mutant called roughex that plays a key role in regulating cell cycle progression in the developing eye (see Materials and Methods;Dong et al 1997). As a consequence of cell cycle defects, photoreceptor differentiation and pattern formation in the eye are disrupted.…”

Section: Loss-of-function Mutations In Ebi and Egfr Have Similar Phenmentioning

confidence: 99%

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ebi regulates epidermal growth factor receptor signaling pathways in Drosophila

Dong¹,

Tsuda²,

Zavitz³

et al. 1999

Genes & Development

118

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ebi regulates the epidermal growth factor receptor (EGFR) signaling pathway at multiple steps in Drosophila development. Mutations in ebi and Egfr lead to similar phenotypes and show genetic interactions. However, ebi does not show genetic interactions with other RTKs (e.g., torso) or with components of the canonical Ras/MAP kinase pathway. ebi encodes an evolutionarily conserved protein with a unique amino terminus, distantly related to F-box sequences, and six tandemly arranged carboxy-terminal WD40 repeats. Epidermal growth factor receptors (EGFRs) have a central role in vertebrate and invertebrate development (for review, see van der Geer et al. 1994;Wassarman et al. 1995;Freeman 1998). Biochemical studies largely in mammalian systems and genetic studies in Caenorhabditis elegans and Drosophila have led to a detailed description of the signal transduction pathways elicited by activation of the EGFR (for review, see Kayne and Sternberg 1995; Schwietzer and Shilo 1997). These include the Ras/MAP kinase (MAPK), Ca 2+ , and phosphatidyl inositol-dependent signaling pathways (for review, see Kazlauskas 1994). In Drosophila, the Ras/MAP kinase cascade is the prominent signaling pathway triggered by the EGFR. Two other fly receptor tyrosine kinases (RTKs) that control patterning and cell fate specification, Torso (for review, see Duffy and Perrimon 1994) and Sevenless (Sev) (for review, see Zipursky and Rubin 1994), do so largely, if not exclusively, through activation of this pathway.The development of the R7 photoreceptor neuron in the fly eye has proved to be a system amenable to detailed genetic dissection of RTK signaling pathways (Wassarman et al. 1995). Whereas the Sev RTK is required for the development of R7 only, EGFR is essential for the development of most, if not all, cells, including R7 (for review, see Freeman 1996a). This dual RTK requirement is intriguing. Constitutively active overexpressed forms of both Sev and EGFR are sufficient to induce R7 development. Furthermore, overexpression of Spitz, a ligand for EGFR, can partially rescue R7 development in a sev null mutant background. These findings have led Freeman (1996b) to propose that signals from Sev and EGFR are qualitatively equivalent. This is consistent with previous findings that overexpression of activated forms of proteins in the Ras/MAP kinase pathway induce receptor-independent R7 development (Fortini et al. 1992;Dickson et al. 1992a;Brunner et al. 1994). These observations support the view that activation of the Ras/MAPK pathway is sufficient to induce R7 development during normal development.The activities of three transcription factors are modulated by the MAPK signaling pathway in the R7 precursor cell. Two ETS-domain-containing transcription factors, Yan and Pointed, are direct targets of MAPK phosphorylation: Pointed is activated by phosphorylation and promotes R7 induction (O'Neil et al. 1994), whereas Yan is inhibited by phosphorylation and acts as a transcriptional repressor (Rebay and Rubin 1995). Inactivation of a second rep...

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“…In Drosophila cells cyclin A is stabilized during S-phase because of the expression of the F-box protein regulator of cyclin A 1 (Rca1), which inhibits APC/C Cdh1 in a non-F-box dependent mechanism (7,8). A vertebrate homologue of Rca1, early mitotic inhibitor 1 (Emi1), was initially identified in Xenopus (9).…”

mentioning

confidence: 99%

Regulation of the Action of Early Mitotic Inhibitor 1 on the Anaphase-promoting Complex/Cyclosome by Cyclin-dependent Kinases

Moshe

Bar-On

Ganoth

et al. 2011

Journal of Biological Chemistry

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Cell cycle regulation is characterized by alternating activities of cyclin-dependent kinases (CDKs) and of the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C). During Sphase APC/C is inhibited by early mitotic inhibitor 1 (Emi1) to allow the accumulation of cyclins A and B and to prevent re-replication. Emi1 is degraded at prophase by a Plk1-dependent pathway. Recent studies in which the degradation pathway of Emi1 was disrupted have shown that APC/C is activated at mitotic entry despite stabilization of Emi1. These results suggested the possibility of additional mechanisms other than degradation of Emi1, which release APC/C from inhibition by Emi1 upon entry into mitosis. In this study we report one such mechanism, by which the ability of Emi1 to inhibit APC/C is negatively regulated by CDKs. We show that in Plk1-inhibited cells Emi1 is stabilized and phosphorylated, that Emi1 is phosphorylated by CDKs in mitotic but not S-phase cell extracts, and that Emi1 phosphorylation by mitotic cell extracts or purified CDKs markedly reduces the ability of Emi1 to bind and to inhibit APC/C. Finally, we show that the addition of extracts from S-phase cells to extracts from mitotic cells protects Emi1 from CDK-mediated inactivation.The eukaryotic cell division is characterized by an ordered unidirectional progression through a series of events culminating in the formation of two genetically identical daughter cells from a single cell. To prevent catastrophes, cell cycle progression must be strictly regulated. In many instances, several mechanisms regulate a single effector or process. Two key mechanisms employed in the regulation of the cell cycle are protein phosphorylation and ubiquitin-mediated protein degradation (1). The family of cyclin-dependent kinases (CDKs) 2 orchestrates numerous events by phosphorylating target proteins throughout the cell cycle. The two principal CDKs implicated in the regulation of the cell cycle are CDK2, which associates with regulatory subunits cyclin E or cyclin A to promote the entry into S-phase and the single replication of the chromosomes, and CDK1, which associates with cyclin A or cyclin B to promote entry into mitosis (2).For cells to enter S-phase and mitosis, cyclins A and B must be allowed to accumulate. Conversely, to exit mitosis, these mitotic cyclins must be rapidly degraded (3). A large multisubunit ubiquitin ligase, the anaphase promoting complex/cyclosome (APC/C) targets cyclins A and B for degradation (4). APC/C is activated upon entry into mitosis due to phosphorylation by mitotic kinases, which promotes the binding of the co-activator Cdc20. Following the metaphase to anaphase transition, APC/C is dephosphorylated and binding of a second co-activator, Cdh1, stimulates APC/C activity until the G 1 -S transition (4). APC/C ubiquitylates cyclin A at prometaphase, shortly after nuclear envelope breakdown, whereas cyclin B is ubiquitylated by APC/C only following bipolar attachment of chromosomes to the mitotic spindle, at the metaphase to anaphase transition (...

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Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A.

Cited by 101 publications

References 56 publications

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

Ectopic expression of cyclin E allows non-endomitotic megakaryoblastic K562 cells to establish re-replication cycles

ebi regulates epidermal growth factor receptor signaling pathways in Drosophila

Regulation of the Action of Early Mitotic Inhibitor 1 on the Anaphase-promoting Complex/Cyclosome by Cyclin-dependent Kinases

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