HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins

Singh, Mahendra; Nicolas, Émmanuelle; Gherraby, Wahiba; Dadke, Disha; Lessin, Stuart R.; Golemis, Erica A.

doi:10.1038/sj.onc.1210282

Cited by 33 publications

(38 citation statements)

References 26 publications

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“…The phenotypes of mice lacking the COSA-1 ortholog, CNTD1, are remarkably similar to those of Hei10 mutants (Holloway et al 2014). Moreover, in somatic cells, human HEI10 interacts with cyclin B1 and can down-regulate cyclin B levels (Toby et al 2003;Singh et al 2007). These data suggest that phosphorylation, driven by a CNTD1/COSA-1-CDK complex, and ubiquitylation, targeted by HEI10, are coupled to effect crossover regulation.…”

Section: Crossover Control Crossover Assurance and Interferencementioning

confidence: 54%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

696

869

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The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans. MEIOSIS AND THE ROOTS OF RECOMBINATION RESEARCHT he concept of recombination emerged during the early 20th century, following the post-Mendel era of heredity research. Thomas Hunt Morgan's formal theory of gene linkage and crossing-over (Morgan 1913) was a synthesis of three key concepts: "the chromosome theory of inheritance," imparted by Wilhelm Roux, Walther Flemming, Theodor Boveri, and Walter Sutton; "gene linkage," an exception to Mendel's law of independent assortment, first reported by Carl Correns; and the "chiasmatype theory," derived from Frans Janssens' cytological observations of meiotic chromosomes. The first proof of the crossover theory came from Harriet Creighton and Barbara McClintock (Creighton and McClintock 1931), who were able to correlate cytological and genetic exchanges in maize.Experiments aimed at understanding the mechanism of meiotic recombination became dominated by fungal genetics because of the huge advantage afforded by being able to recover all four meiotic products. These elegant studies culminated in four key concepts that formed the foundation of molecular models of recombination: gene conversion, an exception to Mendel's principle of segregation, signaled a local nonreciprocal transfer of genetic information (Winkler 1930;Lindergren 1953;Mitchell 1955); postmeiotic segregation (PMS) indicated the presence of heteroduplex DNA (Olive 1959;Kitani et al. 1962) (Lissouba and Rizet 1960;Murray 1960); and the strong correlation between gene conversion/ PMS events and crossing-over led to the proposal that these processes were mechanistically linked (Kitani et al. 1962;Perkins 1962;Whitehouse 1963). MOLECULAR MODELS OF MEIOTIC RECOMBINATIONHolliday's classic model reconciled gene conversion, PMS, and crossing-over into a single mechanism with the key features of hybrid (heteroduplex) DNA formed via strand exchange, mismatch correction of hybrid DNA to yield gene conversion, and a four-way exchange junction that could be resolved to yield either crossover or noncrossover duplex products (Holliday...

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Section: Crossover Control Crossover Assurance and Interferencementioning

confidence: 54%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

696

869

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“…In fact, it has been proposed that rice HEI10 is the functional ortholog of yeast Zip3 and C. elegans ZHP-3 (and, by extension, mammalian RNF212) 71 . However, human HEI10 was reported to have ubiquitin E3 ligase activity (although indirect evidence has associated it with the SUMO pathway) 72,73 , whereas Zip3 and RNF212 seem to be SUMO E3 ligases 31 (Y.Y. and N.H., unpublished data).…”

Section: Discussionmentioning

confidence: 99%

RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis

et al. 2013

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Crossing-over ensures accurate chromosome segregation during meiosis, and every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers. A putative regulator of crossing-over is RNF212, which is associated with variation in crossover rates in humans. We show that mouse RNF212 is essential for crossing-over, functioning to couple chromosome synapsis to the formation of crossover-specific recombination complexes. Selective localization of RNF212 to a subset of recombination sites is shown to be a key early step in the crossover designation process. RNF212 acts at these sites to stabilize meiosis-specific recombination factors, including the MutSγ complex (MSH4-MSH5). We infer that selective stabilization of key recombination proteins is a fundamental feature of meiotic crossover control. Haploinsufficiency indicates that RNF212 is a limiting factor for crossover control and raises the possibility that human alleles may alter the amount or stability of RNF212 and be risk factors for aneuploid conditions.

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“…Previous studies have considered that Hei10 might be important for cancer simply because it regulates (or deregulates) the cell cycle (e.g., Toby et al 2003;Singh et al 2007;Scoles 2008). The current findings, which implicate Hei10 as an integrator and transducer of multiple signal inputs, significantly expand the range of possible roles of Hei10 in cancer.…”

Section: Implications For Hei10's Roles In Mammalian Mitotic Cellsmentioning

confidence: 99%

“…Additionally, involvement of Hei10 with the SPB raises the possibility that a primary target of Hei10-mediated effects for nonmeiotic cells, including cancer cells, could be perturbation of centrosome dynamics with resulting aneuploidy, a central factor in the emergence of the cancerous state. Perturbation of centrosome dynamics could also alter the cell cycle progression, including constraining of cancer cell proliferation (Singh et al 2007;Scoles 2008).…”

Section: Implications For Hei10's Roles In Mammalian Mitotic Cellsmentioning

confidence: 99%

“…It is hyperexpressed in certain cancer cells (Singh et al 2007) but paradoxically can also constrain cancer proliferation (Singh et al 2007;Scoles 2008). Sequence inspection identifies determinants that specify E3 ligase activity and SUMO binding (and thus post-translational modification via ubiquitin/SUMO) and both cyclin binding and cyclin-dependent kinase (CDK) phosphorylation (and thus interplay with the cell cycle) (Supplemental Fig.…”

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confidence: 99%

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E3 ligase Hei10: a multifaceted structure-based signaling molecule with roles within and beyond meiosis

et al. 2014

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Human enhancer of invasion-10 (Hei10) mediates meiotic recombination and also plays roles in cell proliferation. Here we explore Hei10's roles throughout the sexual cycle of the fungus Sordaria with respect to localization and effects of null, RING-binding, and putative cyclin-binding (RXL) domain mutations. Hei10 makes three successive types of foci. Early foci form along synaptonemal complex (SC) central regions. At some of these positions, depending on its RING and RXL domains, Hei10 mediates development and turnover of two sequential types of recombination complexes, each demarked by characteristic amplified Hei10 foci. Integration with ultrastructural data for recombination nodules further reveals that recombination complexes differentiate into three types, one of which corresponds to crossover recombination events during or prior to SC formation. Finally, Hei10 positively and negatively modulates SUMO localization along SCs by its RING and RXL domains, respectively. The presented findings suggest that Hei10 integrates signals from the SC, associated recombination complexes, and the cell cycle to mediate both the development and programmed turnover/evolution of recombination complexes via SUMOylation/ubiquitination. Analogous cell cycle-linked assembly/disassembly switching could underlie localization and roles for Hei10 in centrosome/spindle pole body dynamics and associated nuclear trafficking. We suggest that Hei10 is a unique type of structure-based signal transduction protein.

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HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins

Cited by 33 publications

References 26 publications

Meiotic Recombination: The Essence of Heredity

Meiotic Recombination: The Essence of Heredity

RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis

E3 ligase Hei10: a multifaceted structure-based signaling molecule with roles within and beyond meiosis

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