The Dual Mechanism of Separase Regulation by Securin

Hornig, Nadine; Knowles, Phillip P.; McDonald, Neil Q.; Uhlmann, Frank

doi:10.1016/s0960-9822(02)00847-3

Cited by 136 publications

(166 citation statements)

References 41 publications

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“…Before unleashing separase, cells must ensure that chromosomes are not damaged and that every single one has bi-oriented on the mitotic spindle. Separase is held inactive by its association with a protein called 'securin', (87,88) which is thought to block access to separase's active site at its carboxyterminus (89,90) ( Fig. 6).…”

Section: Establishment Of Cohesion During Dna Replicationmentioning

confidence: 99%

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Building and breaking bridges between sister chromatids

2003

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SummaryEukaryotic chromosomes undergo dramatic changes and movements during mitosis. These include the individualization and compaction of the two copies of replicated chromosomes (the sister chromatids) and their subsequent segregation to the daughter cells. Two multisubunit protein complexes termed 'cohesin' and 'condensin', both composed of SMC (Structural Maintenance of Chromosomes) and kleisin subunits, have emerged as crucial players in these processes. Cohesin is required for holding sister chromatids together whereas condensin, together with topoisomerase II, has an important role in organizing individual axes of sister chromatids prior to their segregation during anaphase. SMC and kleisin complexes also regulate the compaction and segregation of bacterial nucleoids. New research suggests that these ancient regulators of chromosome structure might function as topological devices that trap chromosomal DNA between 50 nm long coiled coils.

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Section: Establishment Of Cohesion During Dna Replicationmentioning

confidence: 99%

“…6). (89,90) Surprisingly, human separase remains inactive after its release from securin in extracts containing high concentrations of undegradeable cyclin B. (93) The inhibition of separase was found to depend on its phosphorylation at a single serine residue.…”

Section: Establishment Of Cohesion During Dna Replicationmentioning

confidence: 99%

Building and breaking bridges between sister chromatids

2003

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“…159,161,162 For most of the cell cycle, separase combines with its inhibitory factor, securin, and loses its ability to dissociate cohesin. 148,[163][164][165] Spindle checkpoint and APC/C control securin dissociation from by adding external MAP kinase. 119 Knockdown of MEK causes misalignment of chromosomes and error in chromosome separation.…”

Section: Spindle Checkpoint Proteins In Mammalian Meiosis Imentioning

confidence: 99%

Molecular insights into mechanisms regulating faithful chromosome separation in female meiosis

Yin

Sun²,

Schatten³

et al. 2008

Cell Cycle

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The faithful segregation of chromosomes into daughter cells in meiosis is crucial to produce healthy progeny. In gametogenesis, two consecutive rounds of chromosome separation occur with only one round of DNA replication, and the chromosome number is reduced to half to produce haploid gametes. Here, we discuss the molecular mechanisms underlying faithful chromosome separation in meiosis from three aspects: spindle checkpoint, two-step releases of cohesion, and the specific space-time protection of cohesin.

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“…Securin plays an essential role in the tightly controlled process of sister-chromatid separation by regulating separase, which cleaves the cohesin complex that binds chromatids together. [9][10][11] While intact, securin supports the nuclear accumulation of separase but inhibits its proteolytic activity. Upon degradation of securin at anaphase onset, separase becomes fully active and promotes the separation of chromatids.…”

Section: Introductionmentioning

confidence: 99%

“…Upon degradation of securin at anaphase onset, separase becomes fully active and promotes the separation of chromatids. 11 The human securin is a protein of 202 amino acids that shows extensive sequence similarity with other vertebrate securins and contains a conserved motif that matches the destruction box (D-box) shared by many APC/C substrates. 12 It is encoded by a gene that is composed of five exons, localises to 5q33 and has been shown to be identical to human pituitarytumour-transforming gene 1.…”

Section: Introductionmentioning

confidence: 99%

High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy

et al. 2003

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High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy Aneuploidy is considered to play an important role in the pathogenesis of malignancies. We were interested whether abnormalities of the sister-chromatid separation regulator and proto-oncogene hSecurin occurred in myeloid leukaemias, and whether such abnormalities correlated with aneuploidy. The expression of hSecurin was assessed by real-time quantitative PCR in samples from patients with acute myeloid leukaemia (AML, n ¼ 70), chronic myeloid leukaemia (CML) in chronic phase (CP, n ¼ 20) or blast phase (BP, n ¼ 12), and granulocytes as well as mononuclear cells (MNCs) from healthy donors (n ¼ 21). Median hSecurin expression in AML with normal karyotypes was not significantly different from AML showing aneuploidy, CML BP or cells from healthy donors. However, hSecurin expression in CML CP was significantly increased compared to AML with normal karyotypes (1.82-fold; Po0.001), CML BP (3.18-fold; Po0.001), MNCs (3.17-fold; Po0.001) and granulocytes (2.69 fold; Po0.001) from healthy donors. Mutations in the coding region of hSecurin were not detected. These results do not support a major role of hSecurin in the development of aneuploidy in myeloid leukaemias. However, high expression of hSecurin may be of pathogenetic relevance in a subset of patients with regard to its potential to stimulate angiogenesis and to interact with the DNA-damage response pathway.

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The Dual Mechanism of Separase Regulation by Securin

Abstract: Securin inhibits the proteolytic activity of separase in a 2-fold manner. While inhibiting separase, securin is able to promote nuclear accumulation of separase and help separase to become fully activated after securin's own destruction at anaphase onset.

Cited by 136 publications

References 41 publications

Building and breaking bridges between sister chromatids

Building and breaking bridges between sister chromatids

Molecular insights into mechanisms regulating faithful chromosome separation in female meiosis

High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy

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