Cyclin-dependent Kinase 1-dependent Phosphorylation of cAMP Response Element-binding Protein Decreases Chromatin Occupancy

Trinh, Anthony T.; Kim, Sang Hwa; Chang, Haeyoon; Mastrocola, Adam M.; Tibbetts, Randal S.

doi:10.1074/jbc.m113.464057

Cited by 12 publications

(6 citation statements)

References 51 publications

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“…HIPK phosphorylation sites of CREB at Ser271 and ATF1 at Ser198 are adjacent to the C-terminal from these KID phosphorylation clusters and localized between the second glutamine-rich (Q2) and basic/b-zip domains. Recently, phosphorylation of CREB at Ser270 and Ser271 by cyclin-dependent kinase 1 (CDK1) during cell cycle G2/M was reported [48]. This seems to be a little different from CREB phosphorylation by HIPK2 because we previously shown that HIPK2 is able to phosphorylate CREB only at Ser271 (ATF1 only at Ser198) [39].…”

Section: Discussionmentioning

confidence: 99%

Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis

Hashimoto

Tsuji

2017

Journal of Molecular Biology

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CREB (cAMP-response element binding protein) plays key transcriptional roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by protein kinase A (PKA) is a well-characterized CREB activation mechanism. HIPK2 (homeodomain interacting protein kinase 2), a nuclear serine/threonine kinase, activates CREB through Ser271 phosphorylation; however, the regulatory mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not Ser133, likewise PKA phosphorylated CREB at Ser133 but not Ser271, suggesting two distinct CREB regulatory mechanisms by HIPK2 and PKA. In vitro kinase assay revealed that HIPK2 as well as HIPK1 and HIPK3 directly phosphorylated CREB. Cells exposed to 10 μM sodium arsenite increased the stability of HIPK1 and HIPK2 proteins leading to CREB activation via Ser271 phosphorylation. Phospho-Ser271 CREB showed facilitated interaction with the TFIID subunit coactivator TAF4 assessed by immunoprecipitation. Furthermore, a focused gene array between cells transfected with CREB alone and CREB plus HIPK2 over empty vector-transfected control displayed 14- and 32-fold upregulation of CCNA1 (cyclin A1), respectively, while no upregulation by HIPK2 alone. These results suggest that the HIPK2-phospho-Ser271 CREB axis is a new arsenic-responsive CREB activation mechanism in parallel with the PKA-phospho-Ser133 CREB axis.

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Section: Discussionmentioning

confidence: 99%

Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis

Hashimoto

Tsuji

2017

Journal of Molecular Biology

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“…The cyclic AMP response element-binding protein (CREB) initiates transcriptional responses associated with cell survival to a wide variety of stimuli following its phosphorylation on Ser-133. Whereas fascaplysin treatment resulted in decreased phosphorylation of CREB in NCI-H526 cells, this transcription factor is hyperphosphorylated in A549 cells, possibly indicating anti- and pro-survival signaling, respectively [ 33 , 34 ]. Furthermore, cisplatin-induced activation of FAK has been linked to increased chemoresistance in ovarian cancer cells and FAK inhibitors induce tumor cell apoptosis [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Fascaplysin against Lung Cancer Cell and Small Cell Lung Cancer Circulating Tumor Cell Lines

et al. 2018

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Lung cancer is a leading cause of tumor-associated mortality. Fascaplysin, a bis-indole of a marine sponge, exhibit broad anticancer activity as specific CDK4 inhibitor among several other mechanisms, and is investigated as a drug to overcome chemoresistance after the failure of targeted agents or immunotherapy. The cytotoxic activity of fascaplysin was studied using lung cancer cell lines, primary Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) cells, as well as SCLC circulating tumor cell lines (CTCs). This compound exhibited high activity against SCLC cell lines (mean IC50 0.89 µM), as well as SCLC CTCs as single cells and in the form of tumorospheres (mean IC50 0.57 µM). NSCLC lines showed a mean IC50 of 1.15 µM for fascaplysin. Analysis of signal transduction mediators point to an ATM-triggered signaling cascade provoked by drug-induced DNA damage. Fascaplysin reveals at least an additive cytotoxic effect with cisplatin, which is the mainstay of lung cancer chemotherapy. In conclusion, fascaplysin shows high activity against lung cancer cell lines and spheroids of SCLC CTCs which are linked to the dismal prognosis of this tumor type. Derivatives of fascaplysin may constitute valuable new agents for the treatment of lung cancer.

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“…Cyclin-dependent kinase 1 (CDK1) is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle progression ( 50 – 53 ). Over 75 proteins, identified as substrates of CDK1 in the budding yeast, are important for cell cycle progression ( 54 – 58 ). Our previous study showed that Sp1 could be phosphorylated by CDK1 at Thr739 to increase its protein stability and decrease its DNA-binding activity.…”

Section: Discussionmentioning

confidence: 99%

Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis

Yang¹,

Chuang²,

Jeng³

et al. 2014

Nucleic Acids Research

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We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis.

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Cyclin-dependent Kinase 1-dependent Phosphorylation of cAMP Response Element-binding Protein Decreases Chromatin Occupancy

Cited by 12 publications

References 51 publications

Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis

Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis

Anticancer Activity of Fascaplysin against Lung Cancer Cell and Small Cell Lung Cancer Circulating Tumor Cell Lines

Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis

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