Drosophila Cyclin D/Cdk4 Requires Hif-1 Prolyl Hydroxylase to Drive Cell Growth

Frei, C.; Edgar, Bruce A.

doi:10.1016/s1534-5807(03)00409-x

Cited by 87 publications

(97 citation statements)

References 39 publications

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“…In parallel, Signaling through TORC1-S6K/4EBP also activates Myc to up-regulate the Cyclin genes [21]. In Drosophila, Cyclin E and Cyclin D drive the endoreplication of larval tissues [22,23]. Consistent with the doubled DNA content, the mRNA levels of Cyclin E and Cyclin D in the [D(+)E(+)] posterior silk gland were ~3-fold higher than in controls ( Figure 4F).…”

Section: Ras Activation Stimulates Ras Downstream Effectorsmentioning

confidence: 90%

Ras1CA overexpression in the posterior silk gland improves silk yield

Zhu

et al. 2011

Cell Res

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Sericulture has been greatly advanced by applying hybrid breeding techniques to the domesticated silkworm, Bombyx mori, but has reached a plateau during the last decades. For the first time, we report improved silk yield in a GAL4/UAS transgenic silkworm. Overexpression of the Ras1 CA oncogene specifically in the posterior silk gland improved fibroin production and silk yield by 60%, while increasing food consumption by only 20%. Ras activation by Ras1 CA overexpression in the posterior silk gland enhanced phosphorylation levels of Ras downstream effector proteins, up-regulated fibroin mRNA levels, increased total DNA content, and stimulated endoreplication. Moreover, Ras1 activation increased cell and nuclei sizes, enriched subcellular organelles related to protein synthesis, and stimulated ribosome biogenesis for mRNA translation. We conclude that Ras1 activation increases cell size and protein synthesis in the posterior silk gland, leading to silk yield improvement.

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Section: Ras Activation Stimulates Ras Downstream Effectorsmentioning

confidence: 90%

Ras1CA overexpression in the posterior silk gland improves silk yield

Zhu

et al. 2011

Cell Res

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“…Many reports show that HiF-1 inhibits the cyclin D [50,16] and the cyclin E [22,19,1] leading to the cell cycle arrest. However, an other report [3] shows that HiF-1 can also stimulate the induction of cyclins D, leading to cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…The second important effect of HiF-1α is the interrelation between this factor and cyclin D [50,16]. Wen et al [50] studied the effect of HiF stabilization on cyclin D level.…”

mentioning

confidence: 99%

“…To confirm the implication of HiF-1, its activity was impaired by DN-HiF overexpression, which induces an increase of the cyclin D level. There is also an action of cyclin D on HiF-1α, due to the activation of the HiF-1 prolyl-hydroxylase activity [16]. Besides, the activation of cyclin D expression by HiF-2 underlines the rivalry in hypoxic tumor growth and progression between HiF-1 and HiF-2.…”

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confidence: 99%

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A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

Bedessem

Stéphanou

2014

Mathematical Biosciences

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Hypoxia is known to influence the cell cycle by increasing the G1 phase duration or by inducing a quiescent state (arrest of cell proliferation). This entry into quiescence is a mean for the cell to escape from hypoxia-induced apoptosis. It is suggested that some cancer cells have gain the advantage over normal cells to easily enter into quiescence when environmental conditions, such as oxygen pressure, are unfavorable [43,1]. This ability contributes in the appearance of highly resistant and aggressive tumor phenotypes [2].The HiF-1α factor is the key actor of the intracellular hypoxia pathway.As tumor cells undergo chronic hypoxic conditions, HiF-1α is present in higher level in cancer than in normal cells. Besides, it was shown that genetic mutations promoting overstabilization of HiF-1α are a feature of various types of cancers [8]. Finally, it is suggested that the intracellular level of HiF-1α can be related to the aggressiveness of the tumors [53,24,4,10] However, up to now, mathematical models describing the G1/S transition under hypoxia, did not take into account the HiF-1α factor in the hypoxia pathway.Therefore, we propose a mathematical model of the G1/S transition under hypoxia, which explicitly integrates the HiF-1α pathway. The model reproduces the slowing down of G1 phase under moderate hypoxia, and the entry into quiescence of proliferating cells under severe hypoxia. We show how the inhibition of cyclin D by HiF-1α can induce quiescence; this result provides a theoretical explanation to the experimental observations of Wen et al. (2010). Thus, our model confirms that hypoxia-induced chemoresistance can be linked, for a part, to the negative regulation of cyclin D by HiF-1α.

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“…57,58 Drosophila PHD is essential for cell growth in fat bodies and wing imaginal discs. 58,59 In humans, heterozygous P317R mutation in PHD2 is associated with moderate polycythemia. 60 P317 is only two amino-acid residues downstream from D315, which directly coordinates Fe(II), 7,10 so P317R mutation likely reduces hydroxylase activity by altering Fe(II) and substrate binding.…”

Section: Biological Functions Of Phdsmentioning

confidence: 99%

Role and regulation of prolyl hydroxylase domain proteins

2008

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Oxygen-dependent hydroxylation of hypoxia-inducible factor (HIF)-a subunits by prolyl hydroxylase domain (PHD) proteins signals their polyubiquitination and proteasomal degradation, and plays a critical role in regulating HIF abundance and oxygen homeostasis. While oxygen concentration plays a major role in determining the efficiency of PHD-catalyzed hydroxylation reactions, many other environmental and intracellular factors also significantly modulate PHD activities. In addition, PHDs may also employ hydroxylase-independent mechanisms to modify HIF activity. Interestingly, while PHDs regulate HIF-a protein stability, PHD2 and PHD3 themselves are subject to feedback upregulation by HIFs. Functionally, different PHD isoforms may differentially contribute to specific pathophysiological processes, including angiogenesis, erythropoiesis, tumorigenesis, and cell growth, differentiation and survival. Because of diverse roles of PHDs in many different processes, loss of PHD expression or function triggers multi-faceted pathophysiological changes as has been shown in mice lacking different PHD isoforms. Future investigations are needed to explore in vivo specificity of PHDs over different HIF-a subunits and differential roles of PHD isoforms in different biological processes.

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Drosophila Cyclin D/Cdk4 Requires Hif-1 Prolyl Hydroxylase to Drive Cell Growth

Cited by 87 publications

References 39 publications

Ras1CA overexpression in the posterior silk gland improves silk yield

Ras1CA overexpression in the posterior silk gland improves silk yield

A mathematical model of HiF-1-mediated response to hypoxia on the G1/S transition

Role and regulation of prolyl hydroxylase domain proteins

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