Protein kinase CK2 links extracellular growth factor signaling with the control of p27Kip1 stability in the heart

Hauck, Ludger; Harms, Christoph; An, Jing; Rohne, J; Gertz, Karen; Dietz, Rainer; Endres, Matthias; Harsdorf, Rüdiger von

doi:10.1038/nm1729

Cited by 99 publications

(105 citation statements)

References 50 publications

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“…Gsk3b is a negative regulator of heart hypertrophy. 33 Interestingly, Hauck 34 recently described that silencing p27 induced cardiomyocyte hypertrophyc growth in the absence of growth-factor stimulation. It is interesting to speculate that Gsk3b mediates negative regulation of hypertrophyc growth through its effects on p27 expression levels.…”

Section: Discussionmentioning

confidence: 99%

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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Akt is a serine-threonine kinase that has an important role in transducing survival signals. Akt also regulates a number of proteins involved in the apoptotic process. To find new Akt interactors, we performed a two-hybrid screening in yeast using full-length Akt cDNA as bait and a human cDNA heart library as prey. Among 200 clones obtained, two of them were identified as coding for the c-FLIP L protein. c-FLIP L is an endogenous inhibitor of death receptor-induced apoptosis through the caspase-8 pathway. Using co-immunoprecipitation experiments of either transfected or endogenous proteins, we confirmed the interaction between Akt and c-FLIP L . Furthermore, we observed that c-FLIP L overexpression interferes with Gsk3-b phosphorylation levels. Moreover, through its effects on Gsk3b, c-FLIP L overexpression in cancer cells induced resistance to tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL). This effect was mediated by the regulation of p27 Kip1 and caspase-3 expression. These results indicate the existence of a new mechanism of resistance to TRAIL in cancer cells, and unexpected functions of c-FLIP L .

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Section: Discussionmentioning

confidence: 99%

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Quintavalle

Incoronato²,

Puca

et al. 2010

Cell Death Differ

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“…The current study highlights an unconventional role for caspases in hypertrophy that does not involve apoptosis. By limiting the duration and degree of caspase activation, CK2 appears central to CT1's nuanced prohypertrophic effects [9], which also involve transient induction of two transcription factors long-recognized to mediate hypertrophy, MEF2 and NFκB. CK2 regulates caspase signaling by phosphorylating both caspase-3 and its targets to inhibit proteolytic cleavage (Figure 1), thus limiting complete execution of the caspase cascade.…”

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confidence: 99%

“…CK2 regulates caspase signaling by phosphorylating both caspase-3 and its targets to inhibit proteolytic cleavage (Figure 1), thus limiting complete execution of the caspase cascade. Of note, CK2 has previously been shown to promote cardiac growth by inhibiting p27, a cell cycle inhibitor [9]. p27 is highly expressed in the heart and downregulated in heart failure.…”

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confidence: 99%

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Size matters: Finding growth pathways that protect the heart

Guseh

Rosenzweig

2017

Cell Res

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“…The MDC provided expertise in basic science, collaborative opportunities, and an infrastructure that existed nowhere else in Germany. As an example, the clinical departments each and independently produced a keynote paper 15 years after their founding [7][8][9][10]. Detlev Ganten's vision of the Robert-Rössle Clinic and the Franz-Volhard Clinic adjacent to the MDC campus could not survive the expediencies of later times.…”

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confidence: 99%

A visionary scientist selects clinicians for clinical research

Luft

2016

J Mol Med

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We celebrate Detlev Ganten's 75th birthday late this March (Fig. 1); we hope he is celebrating too. Detlev Ganten is not only founding editor of the Journal of Molecular Medicine and still active in this capacity, he is also the initial director of the Max-Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. The MDC traces its heritage to the KaiserWilhelm Institute für Hirnforschung, officially founded 1931. The collaboration between Nikolai TimofejewRessovsky, Karl Zimmer, and Max Delbrück that resulted in placing genetics on a molecular footing has been told many times. When the institute was reconstituted after German reunification, Detlev Ganten was given the task of resurrecting the MDC to world-class. And so he did; for 13 years, he was at the helm. Since its founding, 25 years have passed and the MDC has performed even beyond Detlev Ganten's expectations. Of course, since his first two publications appeared in Nature [1] and in Science [2], he probably believes that such publications are easy, as they were for him.Detlev Ganten gave the MDC a unique mission, namely pursuing the highest caliber of disease-oriented (clinical) biological research focusing on the basic mechanisms and molecules of relevance in health and disease and emphasizing the most advanced methodologies in cell biology, genetics, and genomics. He was less interested in the topic and wisely supported the idea that the MDC should pursue a broad spectrum of problems comprising the current chronic scourges, namely cardiovascular disease, cancer, and neurodegenerative disorders. Similarly circumspect, the MDC has maintained this broad base until the present day.Another unique decision Detlev Ganten made was to include clinicians in the field of MDC senior scientists. As the institute had a tradition of encompassing clinical departments since the time of Oskar and Cécile Vogt, the decision was made easier. The institute had continued that tradition and before German reunification had worked intensively with a clinic dedicated to cancer and a clinic for cardiovascular diseases in the framework of the BAcademy of the Sciences^. However, although the clinics were still there, the framework was gone and to continue the concept in conjunction with the two medical schools Berlin had in 1991 was difficult. Furthermore, the mission Detlev Ganten espoused was not necessarily commensurate with the usual department chairmanships in academic medicine. Clinical excellence, teaching, and research were the appropriate criteria of the time; however, Detlev Ganten wanted the order and emphasis revised and reversed. Research at an internationally competitive level was to receive priority, yet the clinical departments also had to work; the patient care had to be excellent, and the teaching mission was not to be ignored. He found his clinicians and the search also underscores the value of personal relationships when making personnel decisions.

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Protein kinase CK2 links extracellular growth factor signaling with the control of p27Kip1 stability in the heart

Cited by 99 publications

References 50 publications

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

c-FLIPL enhances anti-apoptotic Akt functions by modulation of Gsk3β activity

Size matters: Finding growth pathways that protect the heart

A visionary scientist selects clinicians for clinical research

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