The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.

Whitfield, W. G. F.; González, Cayetano; Maldonado-Codina, Gabriela; Glover, David M.

doi:10.1002/j.1460-2075.1990.tb07437.x

Cited by 253 publications

(222 citation statements)

References 49 publications

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“…In order to assess the potential mechanistic basis of the JAK/STAT pathway-induced antiproliferative effect, we stained late Hop misexpressing gain-of-function clones for CycB, a cyclin specifically expressed during the G2 stage of the cell cycle (Whitfield et al, 1990). In such Hop misexpressing clones (which activate STAT92E autonomously), GFP-positive cells contain higher levels of CycB than the surrounding unstimulated cells (Figure 4), indicating that an increased proportion of these cells are in the G2 stage of the cell cycle.…”

Section: Late Jak/stat Activity Causes G2 Arrestmentioning

confidence: 99%

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

2005

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The JAK/STAT signalling pathway mediates both antiproliferative responses following interferon stimulation and cellular proliferation in response to cytokines such as interleukins and growth factors. Central to these responses are the seven vertebrate STAT molecules, misregulation of which is implicated in a variety of malignancies. We have investigated the proliferative role of the single Drosophila STAT92E, part of the evolutionarily conserved JAK/STAT cascade. During second instar larval wing disc development pathway activity is both necessary and sufficient to promote proliferation of this epithelial cell type. However by later stages, endogenous STAT92E is stimulated by a noncannonical mechanism to exert pronounced antiproliferative effects. Ectopic canonical activation is sufficient to further decrease proliferation and leads to the premature arrest of cells in the G2 phase of the cell cycle. The single STAT92E present in Drosophila therefore mediates both proproliferative functions analogous to vertebrate interleukin-stimulated STAT3 and antiproliferative functions analogous to interferon-stimulated STAT1. Pro-and antiproliferative roles therefore represent ancestral activities conserved through evolution and subsequently assigned to distinct molecules.

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Section: Late Jak/stat Activity Causes G2 Arrestmentioning

confidence: 99%

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

2005

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“…Cdk1 (cyclindependent kinase 1) and its binding partner, cyclin B, form a complex essential for entry into mitosis Draetta et al, 1989;Riabowol et al, 1989). Regulation of Cdk1 is achieved by several mechanisms including degradation of cyclin B Whitfield et al, 1990). Cyclin B is targeted for degradation by the proteasome prior to the onset of anaphase by ubiquitin conjugation by the anaphase-promoting complex (APC) (Hershko et al, 1994;King et al, 1995;Yu et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

The Giardia cell cycle progresses independently of the Anaphase Promoting Complex

Gourguechon

Holt

Cande

2013

Journal of Cell Science

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SummaryMost cell cycle regulation research has been conducted in model organisms representing a very small part of the eukaryotic domain. The highly divergent human pathogen Giardia intestinalis is ideal for studying the conservation of eukaryotic pathways. Although Giardia has many cell cycle regulatory components, its genome lacks all anaphase-promoting complex (APC) components. In the present study, we show that a single mitotic cyclin in Giardia is essential for progression into mitosis. Strikingly, Giardia cyclin B lacks the conserved N-terminal motif required for timely degradation mediated by the APC and ubiquitin conjugation. Expression of Giardia cyclin B in fission yeast is toxic, leading to a prophase arrest, and this toxicity is suppressed by the addition of a fission yeast degradation motif. Cyclin B is degraded during mitosis in Giardia cells, but this degradation appears to be independent of the ubiquitination pathway. Other putative APC substrates, aurora and polo-like kinases, also show no evidence of ubiquitination. This is the first example of mitosis not regulated by the APC and might reflect an evolutionary ancient form of cell cycle regulation.

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“…Moreover, activation of the spindle assembly checkpoint, which delays metaphase-anaphase transition until all chromosomes are attached to the mitotic spindles, inhibits cyclin B but not cyclin A degradation. 9,10,[24][25][26] Apart from the differences in timing of proteolysis, the D-box of cyclin A also behaves differently to that of cyclin B. Unlike that of cyclin B, the D-box of cyclin A cannot act as an independent destruction module when grafted onto heterologous proteins.…”

Section: Introductionmentioning

confidence: 99%

The N-terminal Regulatory Domain of Cyclin A Contains Redundant Ubiquitination Targeting Sequences and Acceptor Sites

Fung

Yam²,

Poon³

2005

Cell Cycle

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ACKNOWLEDGEMENTSWe are grateful for Jane Endicott, Tim Hunt and Michele Pagano for generous gifts of reagents. We thank members of the Poon Lab for constructive criticism on the manuscript. This work was supported in part by the Research Grants Council grants HKUST6135/03M and the HKUST grant HIA03/ 04.SC01 to R.Y.C.P.. ReportThe N-Terminal Regulatory Domain of Cyclin A Contains Redundant Ubiquitination Targeting Sequences and Acceptor Sites ABSTRACT Cyclin A is destroyed during mitosis by the ubiquitin-proteasome system. Like cyclin B, a destruction box (D-box) motif is required for the destruction of cyclin A. However, cyclin A degradation is more complicated than cyclin B because cyclin A's D-box motif is more extensive and proteolysis involves complex signaling in some organisms. In this study, we found that in addition to the D-box, the region between residues 123-157 also contributed to the ubiquitination and degradation of human cyclin A. Indeed, removal of the bulk of the N-terminal regulatory domain was needed to completely stabilize cyclin A and eliminate ubiquitination. A putative second RxxL motif around residue 138 played only a minor role in cyclin A degradation. To distinguish between sequences recognized by the ubiquitination machinery and the ubiquitin acceptor sites per se, we utilized a novel approach involving in vitro cleavage of cyclin A after ubiquitination. We found that several lysine residues proximal to the D-box (Lys37, Lys54 and Lys68) were ubiquitin acceptor sites. Cyclin A lacking the three lysine residues was degraded slower than the wild-type protein. Although these lysines were normally used, ubiquitination could shift to other cryptic sites when the preferred sites were unavailable, suggesting the exact positions of the ubiquitin chains also contributed to degradation. Together, these data revealed that ubiquitination does not occur randomly on cyclin A and open up questions on the precise function of the D-box.

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The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.

Cited by 253 publications

References 49 publications

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

Opposing roles for Drosophila JAK/STAT signalling during cellular proliferation

The Giardia cell cycle progresses independently of the Anaphase Promoting Complex

The N-terminal Regulatory Domain of Cyclin A Contains Redundant Ubiquitination Targeting Sequences and Acceptor Sites

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