p62 (SQSTM1) and cyclic AMP phosphodiesterase-4A4 (PDE4A4) locate to a novel, reversible protein aggregate with links to autophagy and proteasome degradation pathways

Frank, Christian; Anthony, Diana F.; Vadrevu, Suryakiran; Riddell, Tracy; Day, Jonathan P.; McLeod, Ruth; Adams, David H.; Baillie, George S.; Houslay, Miles D.

doi:10.1016/j.cellsig.2010.06.003

Cited by 38 publications

(36 citation statements)

References 112 publications

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“…A novel regulatory mechanism was recently proposed, where a membrane-free aggregate containing p62 would form in a rapidly reversible manner facilitating sequestration of specific cargo away from their normal, functionally important sites within the cell. 66 Similar functions of the plant Joka2 protein can be considered, however at present they are too speculative.…”

Section: Discussionmentioning

confidence: 99%

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Identification and functional analysis of Joka2, a tobacco member of the family of selective autophagy cargo receptors

Zientara‐Rytter

Łukomska²,

Moniuszko³

et al. 2011

Autophagy

129

140

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Section: Discussionmentioning

confidence: 99%

“…The first concerns cyclic AMP phosphodiesterase 66 and the secondKeap1 (kelch-like ECH-associated protein 1). 21 Unfortunately, since the molecular function of UP9/LSU is not yet characterized, it is rather difficult to verify the consequences of Joka2 binding.…”

Section: Dna Methods and Plasmids Constructionmentioning

confidence: 99%

Identification and functional analysis of Joka2, a tobacco member of the family of selective autophagy cargo receptors

Zientara‐Rytter

Łukomska²,

Moniuszko³

et al. 2011

Autophagy

129

140

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“…The appropriate activation of autophagy always plays a protective role in response to harmful irritation, such as stress injury and energy depletion [23,[25][26][27]. The activation of autophagy could sequester protein aggresomes and injured organelles to limit the injury [28,29]. The cargoes in the autophagosomes are degraded, and the products were released as substrates of metabolism [28,29].…”

Section: Fangchinoline Induces Energetic Impairment In Bladder Cancermentioning

confidence: 99%

“…The activation of autophagy could sequester protein aggresomes and injured organelles to limit the injury [28,29]. The cargoes in the autophagosomes are degraded, and the products were released as substrates of metabolism [28,29]. However, the excessive activation of autophagy may induce cell death.…”

Section: Fangchinoline Induces Energetic Impairment In Bladder Cancermentioning

confidence: 99%

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Fan¹,

Zhang²,

Ma³

et al. 2017

Cell Physiol Biochem

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Key Words Bladder cancer • Fangchinoline • Autophagy • Apoptosis • ProliferationAbatract Background/Aims: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. Methods and Results: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an upregulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. Conclusions: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.

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“…Some differences exist, however, between these observations in MDA-MB-231 cells and those in CHO cells, in that the redistribution of PDE4A4 into foci in CHO cells occurred upon treatment with rolipram, but not with IBMX [37]. Further studies with the CHO system have shown that the redistribution of PDE4A4 into reversible protein aggregates or foci occurs through its binding to p62, a multi-domain scaffold protein linked to autophagy and proteasome degradation pathways [38][39][40]. Whether this is also true for the redistribution of these PDEs in the MDA-MB-231 cells will need to be determined.…”

Section: Expression Of Pde Protein In Breast Cancer Cell Linesmentioning

confidence: 66%

Inhibition of breast cancer cell migration by activation of cAMP signaling

Dong

Claffey

Brocke

et al. 2015

Breast Cancer Res Treat

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Almost all deaths from breast cancer arise from metastasis of the transformed cells to other sites in the body. Hence, uncovering a means of inhibiting breast cancer cell migration would provide a significant advance in the treatment of this disease. Stimulation of the cAMP signaling pathway has been shown to inhibit migration and motility of a number of cell types. A very effective way of selectively stimulating cAMP signaling is through inhibition of cyclic nucleotide phosphodiesterases (PDEs). Therefore, we examined full expression profiles of all known PDE genes at the mRNA and protein levels in four human breast cancer cell lines and eight patients' breast cancer tissues. By these analyses, expression of almost all PDE genes was seen in both cell lines and tissues. In the cell lines, appreciable expression was seen for PDEs 1C, 2A, 3B, 4A, 4B, 4D, 5A, 6B, 6C, 7A, 7B, 8A, 9A, 10A, and 11A. In patients' tissues, appreciable expression was seen for PDEs 1A, 3B, 4A, 4B, 4C, 4D, 5A, 6B, 6C, 7A, 7B, 8A, 8B, and 9A. PDE8A mRNA in particular is prominently expressed in all cell lines and patients' tissue samples examined. We show here that stimulation of cAMP signaling with cAMP analogs, forskolin, and PDE inhibitors, including selective inhibitors of PDE3, PDE4, PDE7, and PDE8, inhibit aggressive triple negative MDA-MB-231 breast cancer cell migration. Under the same conditions, these agents had little effect on breast cancer cell proliferation. This study demonstrates that PDE inhibitors inhibit breast cancer cell migration, and thus may be valuable therapeutic targets for inhibition of breast cancer metastasis. Since PDE8A is expressed in all breast cancer samples, and since dipyridamole, which inhibits PDE8, and PF-04957325, a selective PDE8 inhibitor, both inhibit migration, it suggests that PDE8A may be a valuable novel target for treatment of this disease.

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p62 (SQSTM1) and cyclic AMP phosphodiesterase-4A4 (PDE4A4) locate to a novel, reversible protein aggregate with links to autophagy and proteasome degradation pathways

Cited by 38 publications

References 112 publications

Identification and functional analysis of Joka2, a tobacco member of the family of selective autophagy cargo receptors

Identification and functional analysis of Joka2, a tobacco member of the family of selective autophagy cargo receptors

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Inhibition of breast cancer cell migration by activation of cAMP signaling

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