Role of CDK/cyclin complexes in transcription and RNA splicing

Loyer, Pascal; Trembley, Janeen H.; Katona, Róbert L.; Kidd, Vincent J.; Lahti, Jill M.

doi:10.1016/j.cellsig.2005.02.005

Cited by 158 publications

(140 citation statements)

References 254 publications

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“…In contrast to its canonical role in the cell cycle as a cofactor for certain cyclin-dependent kinases (CDKs), in other models (58,59), in some cases cyclin D1 acts as a transcriptional coactivator promoting or suppressing gene expression, apparently independently of CDKs (60). Furthermore, certain cyclin-CDK complexes participate in splicing as well as transcription (61) and thus may alter gene expression in cancer cells. In addition to cyclin D1, many growth-promoting genes such as Bcl2-l1, Ccnb1, Ccnd1, Cdk1, and Dhfr also were highly induced in these tumors.…”

Section: Discussionmentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Gene-associated with retinoid-interferon induced mortality-19 (GRIM-19) is an interferon-retinoid–regulated growth suppressor that inhibits cell growth by targeting the transcription factor STAT3 for inhibition. In primary human tumors GRIM-19 is suppressed or mutated, leading to constitutive STAT3 activity and indicating the tumor-suppressive function of GRIM-19. To understand the in vivo role of Grim-19 in tumor development, we generated a Grim-19 conditional knockout mouse. We found that deletion of even a single Grim-19 allele is sufficient to augment skin tumorigenesis in mice, thus establishing a critical role for Grim-19 as a tumor suppressor. Tumors that developed in the absence of Grim-19 exhibited mitochondrial respiratory chain dysfunction, elevated glycolysis, and Stat3-responsive gene expression.

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Section: Discussionmentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Centrosomes were enriched from asynchronously growing log-phase U2OS cell cultures by subcellular fractionation and discontinuous sucrose gradient centrifugation as described by Bornens and Moudjou [61,64]. (A) Immunoblot analysis shows particulate material from sucrose gradient fractions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), which was spun through a 1 ml buffer cushion. The arrow scale below the blot indicates the direction and the percentage of the sucrose gradient concentration.…”

Section: Discussionmentioning

confidence: 99%

“…All cyclins possess a characteristic "cyclin fold" containing highly conserved alpha-helical sequence regions referred to as the cyclin box and a bundle repeat [2,3]. Despite structural similarities, some cyclins and CDKs are associated with functions not directly linked to cell cycle progression, e.g., transcription and neurite outgrowth [4][5][6]. Cyclin G2, (G2) is an unconventional cyclin [7,8] expressed at modest levels in proliferating cells, peaking during the late S/early G 2 -phase, that is significantly upregulated as cells exit the cell cycle in response to DNA damage and receptor mediated negative signaling in B-lymphocytes [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

Don

Dallapiazza

Bennin

et al. 2006

Experimental Cell Research

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Cyclin G2 is an atypical cyclin that associates with active protein phosphatase 2A. Cyclin G2 gene expression correlates with cell cycle inhibition; it is significantly upregulated in response to DNA damage and diverse growth inhibitory stimuli, but repressed by mitogenic signals. Ectopic expression of cyclin G2 promotes cell cycle arrest, cyclin dependent kinase 2 inhibition, and the formation of aberrant nuclei [1]. Here we report that endogenous cyclin G2 copurifies with centrosomes and microtubules (MT), and that ectopic G2 expression alters microtubule stability. We find exogenous and endogenous cyclin G2 present at microtubule organizing centers (MTOCs) where it colocalizes with centrosomal markers in a variety of cell lines. We previously reported that cyclin G2 forms complexes with active protein phosphatase 2A (PP2A) and colocalizes with PP2A in a detergent resistant compartment. We now show that cyclin G2 and PP2A colocalize at MTOCs in transfected cells, and that the endogenous proteins copurify with isolated centrosomes. Displacement of the endogenous centrosomal scaffolding protein AKAP450 that anchors PP2A at the centrosome, resulted in the depletion of centrosomal cyclin G2. We find that ectopic expression of cyclin G2 induces microtubule bundling and resistance to depolymerization, inhibition of polymer regrowth from MTOCs, and a p53 dependent cell cycle arrest. Furthermore, we determined that a 100 amino acid carboxy-terminal region of cyclin G2 is sufficient to both direct GFP localization to centrosomes and induce cell cycle inhibition. Colocalization of endogenous cyclin G2 with only one of two GFPcentrin tagged centrioles, the mature centriole present at microtubule foci, indicate that cyclin G2 resides primarily on the mother centriole. Copurification of cyclin G2 and PP2A subunits with microtubules and centrosomes, together with the effects of ectopic cyclin G2 on cell cycle progression, nuclear morphology, and microtubule growth and stability, suggests that cyclin G2 may modulate the cell cycle and cellular division processes through modulation of PP2A and centrosomal associated activities.

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“…The kinase has been found complexed with two cyclins, Cyclin T and Cyclin K. The kinase subunit forms the catalytic core of positive transcription elongation factor b (p-TEFb) [44][45][46][47]. It plays a crucial role in increasing transcriptional elongation from RNA Pol II-dependent promoters, including many key developmental and response genes, as well as the vast majority of protein coding genes [48].…”

Section: Cdk9mentioning

confidence: 99%

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

Zhelev

Trifonov²,

Wang³

et al. 2013

Biodiscovery

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This monograph reviews the discovery and development of the cyclindependent kinase inhibitor roscovitine (R-roscovitine, CYC202, Seliciclib). The authors summarise the in vitro and in vivo data that have formed the basis for clinical investigation of Seliciclib as an anti-cancer drug. Kinase selectivity, cellular effects and the pharmacological properties of the drug are discussed in addition to the clinical results of Seliciclib being reviewed. Novel results on the effect of the drug in cardiac hypertrophy are summarized and potential applications of Seliciclib in other therapeutic areas, including, inflammation, virology, glomerulonephritis and polycystic kidney disease, are discussed. Finally the authors argue that optimisation of the therapeutic effect of kinase inhibitors such as Seliciclib can be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. Seliciclib -discovery and developmentBioDiscovery 2 December 2013 | Issue 10 | 1

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Role of CDK/cyclin complexes in transcription and RNA splicing

Cited by 158 publications

References 254 publications

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

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