Checking out the G2/M transition

Smits, Veronique A. J.; Medema, René H.

doi:10.1016/s0167-4781(01)00204-4

Cited by 323 publications

(279 citation statements)

References 180 publications

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“…Significantly, cyclin-dependent kinase activity is essential for maintaining the integrity of the mitotic spindle checkpoint. The apparent preferential colocalization of TSPY protein with cyclin B1, CDK1 at the mitotic spindles of the metaphase cells suggests that TSPY could affect the cyclin B1-CDK1 functions on the spindles (Pines and Hunter, 1992;Richter, 2001;Smits and Medema, 2001;Porter and Donoghue, 2003;Wang et al, 2004b;Fukasawa, 2007), thereby disrupting this mitotic checkpoint that could potentially result in chromosome nondisjunction and aneuploidy. Indeed, precursors of testicular germ cell tumors, that is, CIS/ITGCNU, could express TSPY at relatively high levels, whereas the resulting TGCTs are usually aneuploid (Looijenga and Oosterhuis, 2002;Oosterhuis and Looijenga, 2005;Rajpert-De Meyts, 2006), thereby supporting the notation that overexpression of TSPY could increase genomic instability.…”

Section: Discussionmentioning

confidence: 99%

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Lau

2008

Oncogene

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Testis-specific protein Y-encoded (TSPY) is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). TSPY and an X-homologue, TSPX, harbor a conserved domain, designated as SET/NAP domain, but differ at their C termini. Ectopic expression of TSPY accelerates cell proliferation by abbreviating the G 2 /M stage, whereas overexpression of TSPX retards cells at the same stage of the cell cycle. Previous studies demonstrated that the SET oncoprotein is capable of binding to cyclin B. Using various protein interaction techniques, we demonstrated that TSPY and TSPX indeed bind competitively to cyclin B at their SET/NAP domains in vitro and in vivo. TSPY colocalizes with cyclin B1 during the cell cycle, particularly on the mitotic spindles at metaphase. TSPY enhances while TSPX represses the cyclin B1-CDK1 phosphorylation activity. The inhibitory effect of TSPX on the cyclin B1-CDK1 complex has been mapped to its carboxyl acidic domain that is absent in TSPY, suggesting that TSPX could serve a normal function in modulating cell-cycle progression at the G 2 /M stage, whereas TSPY has acquired a specialized function in germ cell renewal and differentiation. Epigenetic dysregulation of TSPY in incompatible germ or somatic cells could promote cell proliferation and predispose susceptible cells to tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Lau

2008

Oncogene

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“…30,31 The second checkpoint is at the G2/M phase transition and controls mitosis and cell division. 32 When Figure 6 The expression, threonine phosphorylation, and localization of p27 Kip1 are regulated through the PI3K/Akt pathway. The subcellular localization of p27 Kip1 is under the control of the PI3K/Akt axis.…”

Section: Discussionmentioning

confidence: 99%

The phosphoinositide 3-kinase/Akt pathway regulates cell cycle progression of HL60 human leukemia cells through cytoplasmic relocalization of the cyclin-dependent kinase inhibitor p27Kip1 and control of cyclin D1 expression

et al. 2003

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The serine/threonine protein kinase Akt, a downstream effector of phosphoinositide 3-kinase (PI3K), plays a pivotal role in tumorigenesis because it affects the growth and survival of cancer cells. Several laboratories have demonstrated that Akt inhibits transcriptional activation of a number of related forkhead transcription factors now referred to as FoxO1, FoxO3, and FoxO4. Akt-regulated forkhead transcription factors are involved in the control of the expression of both the cyclindependent kinase (cdk) inhibitor p27 Kip1 and proapoptotic Bim protein. Very little information is available concerning the importance of the PI3K/Akt pathway in HL60 human leukemia cells. Here, we present our findings showing that the PI3K/Akt axis regulates cell cycle progression of HL60 cells through multiple mechanisms also involving the control of FoxO1 and FoxO3. To this end, we took advantage of a HL60 cell clone (HL60AR cells) with a constitutively activated PI3K/Akt axis. When compared with parental (PT) HL60 cells, HL60AR cells displayed higher levels of phosphorylated FoxO1 and FoxO3. In AR cells forkhead factors localized predominantly in the cytoplasm, whereas in PT cells they were mostly nuclear. AR cells proliferated faster than PT cells and showed a lower amount of the cdk inhibitor p27 Kip1 , which was mainly found in the cytoplasm and was hyperphosphorylated on threonine residues. AR cells also displayed higher levels of cyclin D1 and phosphorylated p110 Retinoblastoma protein. The protein levels of cdk2, cdk4, and cdk6 were not altered in HL60AR cells, whereas the activities of both ckd2 and cdk6 were higher in AR than in PT cells. These results show that in HL60 cells the PI3K/Akt signaling pathway may be involved in the control of the cell cycle progression most likely through mechanisms involving the activation of forkhead transcription factors.

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“…7 In addition to regulation through its association with cyclin B, both activating and inactivating phosphorylations are required to modulate Cdc2 activity. In mammalian cells, the activating phosphorylation of Cdc2 at threonine 161 (T161) in the T-loop is catalyzed by Cdc2 activating kinase, (CAK; Cdc7/cyclinH) and CAK activity is quite constant throughout the cell cycle.…”

confidence: 99%

Knockdown of Chk1, Wee1 and Myt1 by RNA Interference Abrogates G2 Checkpoint and Induces Apoptosis

Wang¹,

Decker²,

Sebolt–Leopold³

2004

Cancer Biology & Therapy

124

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Checking out the G2/M transition

Cited by 323 publications

References 180 publications

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

The phosphoinositide 3-kinase/Akt pathway regulates cell cycle progression of HL60 human leukemia cells through cytoplasmic relocalization of the cyclin-dependent kinase inhibitor p27Kip1 and control of cyclin D1 expression

Knockdown of Chk1, Wee1 and Myt1 by RNA Interference Abrogates G2 Checkpoint and Induces Apoptosis

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