Imaging Centrosomes in Fly Testes

Centrosomes are conserved microtubule-based organelles whose structure and function change dramatically throughout the cell cycle and cell ...

University of Toledo

Human Papillomavirus (HPV) E2 proteins are the major viral regulators of transcription and replication during the viral life cycle. In addition to these conserved functions, we show that E2 proteins from high risk HPV types 16 and 18, which are associated with cervical cancer, can induce apoptosis. In contrast, E2 proteins from low risk HPV types 6 and 11, which are associated with benign lesions, do not cause cell death. We show that the ability to induce apoptosis is linked to the intracellular localization of the respective E2 proteins rather than to inherent properties of the proteins. Although low risk HPV E2 proteins remain strictly nuclear, high risk HPV E2 proteins are present in both the nucleus and the cytoplasm of expressing cells due to exportin-1 receptor (CRM1)-dependent nucleo-cytoplasmic shuttling. Induction of apoptosis is caused by accumulation of E2 in the cytoplasm and involves caspase 8 activation. We speculate that disruption of the E2 gene during viral genome integration in cervical carcinoma provides a means to avoid E2-induced apoptosis and allow initiation of carcinogenesis.

Nucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis.

Les prot&eacute;ines humaines de Papillomavirus (HPV) E2 sont les principaux r&eacute;gulateurs virales de la transcription et la r&eacute;plication au cours du cycle de vie viral. Outre ces fonctions conserv&eacute;es, nous montrent que les prot&eacute;ines E2 de risque &eacute;lev&eacute; VPH des types 16 et 18, qui sont associ&eacute;s au cancer du col ut&eacute;rin, peuvent induire l&#39;apoptose. En revanche, prot&eacute;ines E2 de faible risque VPH des types 6 et 11 qui sont associ&eacute;es &agrave; des l&eacute;sions b&eacute;nignes, ne provoquent pas la mort des cellules. Nous montrons que la capacit&eacute; d&#39;induire l&#39;apoptose est li&eacute;e &agrave; la localisation intracellulaire des prot&eacute;ines E2 respectifs, plut&ocirc;t qu&#39;aux propri&eacute;t&eacute;s inh&eacute;rentes des prot&eacute;ines. Bien que les prot&eacute;ines de faible risque HPV E2 restent strictement nucl&eacute;aires, prot&eacute;ines de haut risque de HPV E2 sont pr&eacute;sents dans le noyau et le cytoplasme d&#39;exprimer des cellules en raison de l&#39;exportation-1 receptor (CRM1)-d&eacute;pendante la navette nucl&eacute;o-cytoplasmique. Induction de l&#39;apoptose est caus&eacute;e par l&#39;accumulation de E2 dans le cytoplasme et implique l&#39;activation de la caspase 8. Nous sp&eacute;culons que perturbation du g&egrave;ne E2 au cours de l&#39;int&eacute;gration du g&eacute;nome viral dans le carcinome du col ut&eacute;rin constitue un moyen d&#39;&eacute;viter l&#39;apoptose induite par l&#39;E2 et de permettre l&#39;initiation de la canc&eacute;rogen&egrave;se.

La navette nucl&eacute;o-cytoplasmique de prot&eacute;ines humaines de Papillomavirus E2 risque &eacute;lev&eacute; induit l&#39;apoptose.

Proteine umane di Papillomavirus (HPV) E2 sono i principali regolatori virali della trascrizione e replica durante il ciclo di vita virale. Oltre a queste funzioni conservate, ci mostra che le proteine E2 da tipi di HPV ad alto rischio 16 e 18, che sono associati con cancro cervicale, possono indurre il apoptosis. Proteine E2 da tipi di HPV a basso rischio 6 e 11, che sono associati a lesioni benigne, in contrasto, non causano la morte delle cellule. Mostriamo che la capacit&agrave; di indurre l&#39;apoptosi &egrave; legata alla localizzazione intracellulare delle rispettive proteine E2, piuttosto che alle propriet&agrave; intrinseche delle proteine. Anche se le proteine E2 di HPV a basso rischio restano rigorosamente nucleare, proteine ad alto rischio HPV E2 sono presenti in entrambi il nucleo e del citoplasma delle cellule dovuto exportin-1 receptor (CRM1) di esprimere-dipendente nucleo-citoplasmatici spola. Induzione di apoptosi &egrave; causato dall&#39;accumulo di E2 nel citoplasma e coinvolge l&#39;attivazione di caspase 8. Si ipotizzano che turbativa del gene E2 durante l&#39;integrazione del genoma virale nel carcinoma cervicale consente di evitare l&#39;apoptosi indotta da E2 e consentire l&#39;avvio della cancerogenesi.

Nucleo-citoplasmatici spola di proteine Papillomavirus E2 umane ad alto rischio induce l&#39;apoptosi.

Human papillomaviruses (HPVs) from the high-risk group are associated with cervical cancer, in contrast to HPVs from the low-risk group which are associated with benign lesions of the genital tract. Here, we show that high-risk, but not low-risk HPV E2 proteins, promote a mitotic block, often followed by metaphase-specific apoptosis, and which is independent of the viral oncogenes E6 and E7. High-risk HPV E2-expressing cells also show polyploidy, chromosomal mis-segregation and centrosome amplification leading to genomic instability. We link these defects to a specific and unusually strong interaction between high-risk E2 and both Cdc20 and Cdh1, two activators of the Anaphase Promoting Complex (APC), abnormal localization of Cdh1, and accumulation of APC substrates like cyclin B, in vivo. The finding that high-risk, but not low-risk HPV E2 proteins, induce genomic instability, raises the intriguing possibility that E2 proteins play a role in the oncogenic potential of high-risk papillomaviruses.

High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and Cdc20 and cause genomic instability.

&#x4E2D;&#x5FC3;&#x7C92;&#x662F;&#x4E2D;&#x5FC3;&#x4F53;&#x548C;&#x7EA4;&#x6BDB;&#x7684;&#x6838;&#x5FC3;&#x7ED3;&#x6784;&#x3002;&#x9650;&#x5236;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x590D;&#x5236;&#x5230;&#x6BCF;&#x4E2A;&#x7EC6;&#x80DE;&#x5468;&#x671F;&#x7684;&#x4E00;&#x6B21;&#x5931;&#x8D25;&#x5E26;&#x6765;&#x4E25;&#x91CD;&#x7684;&#x540E;&#x679C;&#xFF0C;&#x901A;&#x5E38;&#x5728;&#x764C;&#x75C7;&#x4E2D;&#x89C2;&#x5BDF;&#x5230;&#x3002;&#x5C3D;&#x7BA1;&#x5176;&#x533B;&#x7597;&#x7684;&#x91CD;&#x8981;&#x6027;&#xFF0C;&#x4E2D;&#x5FC3;&#x7C92;&#x7684;&#x5F62;&#x6210;&#x673A;&#x7406;&#x662F;&#x751A;&#x5C11;&#x3002;Asl &#x4EE5;&#x524D;&#x636E;&#x8BF4; centrosomal &#x86CB;&#x767D;&#x8D28;&#x4E2D;&#x5FC3;&#x4F53;&#x529F;&#x80FD;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x627E;&#x51FA; mecD&#xFF0C;&#x4E25;&#x91CD;&#x635F;&#x5931;&#x7684;&#x51FD;&#x6570;&#x7B49;&#x4F4D;&#x57FA;&#x56E0;&#x7684; asl &#x57FA;&#x56E0;&#xFF0C;&#x5E76;&#x8BC1;&#x660E;&#x5B83;&#x662F;&#x5FC5;&#x9700;&#x7684;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x548C;&#x7EA4;&#x6BDB;&#x5F62;&#x6210;&#x3002;&#x540C;&#x6837;&#xFF0C;Cep152&#xFF0C;&#x5728;&#x810A;&#x690E;&#x52A8;&#x7269;&#xFF0C;&#x7FD4;&#x5347; ortholog &#x7EA4;&#x6BDB;&#x5F62;&#x6210;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#xFF0C;&#x5176;&#x529F;&#x80FD;&#x53EF;&#x4EE5;&#x7531;&#x679C;&#x8747;&#x7FD4;&#x5347;&#x90E8;&#x5206;&#x6551;&#x51FA;&#x3002;Asl &#x5B9A;&#x4F4D;&#x7684;&#x7814;&#x7A76;&#x8868;&#x660E;&#x5B83;&#x4E0E;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x9694;&#x79BB;&#x5899;&#xFF0C;&#x5BC6;&#x5207;&#x5173;&#x8054;&#xFF0C;&#x4F46;&#x4E0D;&#x662F;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x7ED3;&#x6784;&#x7684;&#x4E00;&#x90E8;&#x5206;&#x3002;&#x901A;&#x8FC7;&#x5206;&#x6790;&#x751F;&#x7269;&#x7EC6;&#x80DE;&#x8017;&#x5C3D;&#x7684; Asl &#x4E2D;&#x5FC3;&#x4F53;&#x7684;&#x53D1;&#x751F;&#xFF0C;&#x6211;&#x4EEC;&#x53D1;&#x73B0;&#xFF0C;&#x867D;&#x7136; pericentriolar &#x6750;&#x6599; (PCM) &#x529F;&#x80FD;&#x8F7B;&#x5EA6;&#x53D7;&#x5F71;&#x54CD;&#xFF0C;Asl &#x662F;&#x5973;&#x513F;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x5F62;&#x6210;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;&#x7F3A;&#x4E4F;&#x660E;&#x786E;&#x7684;&#x51E0;&#x4E2A; mecD &#x7A81;&#x53D8;&#x4F53;&#x7684; centriolar &#x6807;&#x8BB0;&#x8868;&#x660E; Asl &#x662F;&#x65E9;&#x671F;&#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x91CD;&#x590D;&#x7684;&#x5173;&#x952E;&#x3002;

&#x679C;&#x8747; asterless &#x548C;&#x810A;&#x690E;&#x52A8;&#x7269; Cep152 &#x662F; orthologs &#x7EC6;&#x80DE;&#x5668;&#x8FDB;&#x884C;&#x91CD;&#x590D;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;

The centriole is the core structure of centrosome and cilium. Failure to restrict centriole duplication to once per cell cycle has serious consequences and is commonly observed in cancer. Despite its medical importance, the mechanism of centriole formation is poorly understood. Asl was previously reported to be a centrosomal protein essential for centrosome function. Here we identify mecD, a severe loss-of-function allele of the asl gene, and demonstrate that it is required for centriole and cilia formation. Similarly, Cep152, the Asl ortholog in vertebrates, is essential for cilia formation and its function can be partially rescued by the Drosophila Asl. The study of Asl localization suggests that it is closely associated with the centriole wall, but is not part of the centriole structure. By analyzing the biogenesis of centrosomes in cells depleted of Asl, we found that, while pericentriolar material (PCM) function is mildly affected, Asl is essential for daughter centriole formation. The clear absence of several centriolar markers in mecD mutants suggests that Asl is critical early in centriole duplication.

Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication.

Le centriole est la structure de base de centrosome et cil. Impossibilit&#xE9; de limiter la duplication de centriole cycle cellulaire une fois par a de graves cons&#xE9;quences et il est couramment observ&#xE9; dans le cancer. En d&#xE9;pit de son importance m&#xE9;dicale, le m&#xE9;canisme de formation centriole est mal comprise. Asl a &#xE9;t&#xE9; pr&#xE9;c&#xE9;demment d&#xE9;clar&#xE9;e &#xE0; une prot&#xE9;ine essentielle pour la fonction centrosomale centrosome. Ici nous identifions MECD, une grave perte de la fonction all&#xE8;le du g&#xE8;ne d&#x26;#39;altitude, et de d&#xE9;montrer qu&#x26;#39;elle est n&#xE9;cessaire pour centriole et la formation de cils. De m&#xEA;me, Cep152, l&#x26;#39;orthologue Asl chez les vert&#xE9;br&#xE9;s, est essentiel pour la formation des cils et sa fonction peut &#xEA;tre partiellement sauv&#xE9; par l&#x26;#39;Asl drosophile. L&#x26;#39;&#xE9;tude de la localisation Asl sugg&#xE8;re qu&#x26;#39;il est &#xE9;troitement associ&#xE9; &#xE0; la paroi centriole, mais ne fait pas partie de la structure centriole. En analysant la biogen&#xE8;se des centrosomes dans les cellules appauvries de l&#x26;#39;ASL, nous avons constat&#xE9; que, tandis que p&#xE9;ricentriolaire mat&#xE9;riau (PCM) est fonction l&#xE9;g&#xE8;rement touch&#xE9;s, Asl est essentiel pour la formation de centriole fille. L&#x26;#39;absence claire de plusieurs marqueurs dans centriolaires mutants MECD sugg&#xE8;re que Asl est essentiel au d&#xE9;but de centriole duplication.

Drosophila Asterless et des vert&#xE9;br&#xE9;s Cep152 Etes Orthologues Indispensable pour Centriole Duplication

Die Zentriol ist die Kernstruktur des Zentrosom und Zilie. Zentriol Vervielf&auml;ltigung auf einmal pro Zellzyklus zu beschr&auml;nken hat ernste Konsequenzen und wird h&auml;ufig bei Krebs beobachtet. Trotz der medizinischen Bedeutung wird der Mechanismus der Zentriol Bildung schlecht verstanden. ASL wurde zuvor berichtet, ein centrosomal Protein, das f&uuml;r Zentrosom Funktion wesentlich zu sein. Hier erkennen wir MecD, einen schweren Verlust of Function-Allel des Gens asl, und zeigen, dass es f&uuml;r Zentriol und Zilien Bildung erforderlich ist. Ebenso Cep152, die Asl-Ortholog bei Wirbeltieren, ist essentiell f&uuml;r Zilien Bildung und seine Funktion kann teilweise von der Drosophila-Asl gerettet werden. Das Studium der Asl Lokalisierung legt nahe, dass es eng verbunden mit der Wand Zentriol ist, aber nicht Teil der Zentriol-Struktur ist. Durch die Analyse der Biogenese Centrosomes in Zellen, die Asl ausgelaugt, fanden wir, dass w&auml;hrend Pericentriolar materiell (PCM) Funktion leicht betroffen ist, ist Asl f&uuml;r Tochter Zentriol Bildung wichtig. Die klare mehrere centriolar Marker in MecD Mutanten nahe, dass Asl fr&uuml;h in Zentriol Duplikation ankommt.

Taufliege asterless und vertebrate Cep152 sind Orthologen notwendig f&uuml;r Zentriol Vervielf&auml;ltigung.

Il Centriolo &egrave; la struttura di base del centrosoma e cilio. Fallimento per limitare la duplicazione di una volta per ciclo cellulare Centriolo ha gravi conseguenze ed &egrave; comunemente osservato nel cancro. Nonostante la sua importanza medica, il meccanismo di formazione Centriolo &egrave; scarsamente compreso. ASL in precedenza &egrave; stato segnalato per essere una proteina centrosomal essenziale per la funzione centrosoma. Qui ci identifichiamo mecD, un grave perdita della funzione allele del gene della asl e dimostrare che &egrave; necessaria per la formazione Centriolo e le ciglia. Analogamente, Cep152, l&#39;Asl ortholog nei vertebrati, &egrave; essenziale per la formazione di ciglia e la sua funzione pu&ograve; essere parzialmente salvata dall&#39;Asl della drosofila. Lo studio della localizzazione Asl suggerisce che esso &egrave; strettamente associato con il muro Centriolo, ma non &egrave; parte della struttura del Centriolo. Analizzando la biogenesi di cntrosome nelle cellule impoverite di Asl, abbiamo scoperto che, mentre la funzione (PCM) materiale pericentriolar &egrave; leggermente influenzato, Asl &egrave; essenziale per la formazione di figlia Centriolo. La chiara assenza di diversi marcatori centriolar mecD mutanti suggerisce che la Asl &egrave; critico all&#39;inizio della duplicazione Centriolo.

Drosofila vertebrati e asterless Cep152 sono orthologs essenziali per la duplicazione Centriolo.

&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x306F;&#x4E2D;&#x5FC3;&#x4F53;&#x3068;&#x7E4A;&#x6BDB;&#x306E;&#x30B3;&#x30A2;&#x69CB;&#x9020;&#x3067;&#x3059;&#x3002; 1&#x56DE;&#x306E;&#x7D30;&#x80DE;&#x5468;&#x671F;&#x306B;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x306E;&#x8907;&#x88FD;&#x3092;&#x5236;&#x9650;&#x3059;&#x308B;&#x969C;&#x5BB3;&#x304C;&#x6DF1;&#x523B;&#x306A;&#x5F71;&#x97FF;&#x3092;&#x6301;&#x3063;&#x3066;&#x304A;&#x308A;&#x3001;&#x4E00;&#x822C;&#x7684;&#x306A;&#x764C;&#x3067;&#x89B3;&#x5BDF;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x305D;&#x306E;&#x533B;&#x7642;&#x306E;&#x91CD;&#x8981;&#x6027;&#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x3001;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x5F62;&#x6210;&#x306E;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306F;&#x3042;&#x307E;&#x308A;&#x7406;&#x89E3;&#x3055;&#x308C;&#x3066;&#x3044;&#x306A;&#x3044;&#x3002; ASL&#x306F;&#x3001;&#x4EE5;&#x524D;&#x306B;&#x4E2D;&#x5FC3;&#x4F53;&#x6A5F;&#x80FD;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x306A;&#x4E2D;&#x5FC3;&#x4F53;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x304C;&#x5831;&#x544A;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;mecD&#x3001;ASL&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x6DF1;&#x523B;&#x306A;&#x6A5F;&#x80FD;&#x55AA;&#x5931;&#x578B;&#x5BFE;&#x7ACB;&#x907A;&#x4F1D;&#x5B50;&#x3092;&#x8B58;&#x5225;&#x3057;&#x3001;&#x305D;&#x308C;&#x306F;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x3068;&#x7E4A;&#x6BDB;&#x5F62;&#x6210;&#x306B;&#x5FC5;&#x8981;&#x3068;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x540C;&#x69D8;&#x306B;&#x3001;Cep152&#x3001;&#x810A;&#x690E;&#x52D5;&#x7269;&#x306B;&#x304A;&#x3051;&#x308B;ASL&#x30AA;&#x30EB;&#x30BD;&#x30ED;&#x30B0;&#x306F;&#x3001;&#x7E4A;&#x6BDB;&#x306E;&#x5F62;&#x6210;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3042;&#x308A;&#x3001;&#x305D;&#x306E;&#x6A5F;&#x80FD;&#x306F;&#x90E8;&#x5206;&#x7684;&#x306B;&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;ASL&#x306B;&#x3088;&#x3063;&#x3066;&#x6551;&#x52A9;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002; ASL&#x5C40;&#x5728;&#x306E;&#x7814;&#x7A76;&#x306F;&#x3001;&#x305D;&#x308C;&#x304C;&#x5BC6;&#x63A5;&#x306B;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x306E;&#x58C1;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x304C;&#x3001;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x69CB;&#x9020;&#x306E;&#x4E00;&#x90E8;&#x3067;&#x306F;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x3002; ASL&#x306E;&#x67AF;&#x6E07;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B;&#x4E2D;&#x5FC3;&#x4F53;&#x306E;&#x751F;&#x5408;&#x6210;&#x3092;&#x5206;&#x6790;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;&#x6211;&#x3005;&#x306F;&#x4E2D;&#x5FC3;&#x4F53;&#x5468;&#x8FBA;&#x7269;&#x8CEA;&#xFF08;PCM&#xFF09;&#x95A2;&#x6570;&#x306F;&#x3001;&#x8EFD;&#x5EA6;&#x306E;&#x5F71;&#x97FF;&#x3092;&#x53D7;&#x3051;&#x3066;&#x3044;&#x308B;&#x9593;&#x306B;&#x3001;ASL&#x304C;&#x5A18;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x5F62;&#x6210;&#x306E;&#x305F;&#x3081;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x304C;&#x308F;&#x304B;&#x3063;&#x305F;&#x3002; mecD&#x5909;&#x7570;&#x4F53;&#x306E;&#x3044;&#x304F;&#x3064;&#x304B;&#x306E;centriolar&#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x306E;&#x660E;&#x78BA;&#x306A;&#x6B20;&#x5982;&#x306F;&#x3001;ASL&#x304C;&#x65E9;&#x671F;&#x306B;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x306E;&#x8907;&#x88FD;&#x306B;&#x91CD;&#x8981;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;

&#x30B7;&#x30E7;&#x30A6;&#x30B8;&#x30E7;&#x30A6;&#x30D0;&#x30A8;Asterless&#x3068;&#x810A;&#x690E;&#x52D5;&#x7269;Cep152&#x306F;&#x4E2D;&#x5FC3;&#x5C0F;&#x4F53;&#x306E;&#x8907;&#x88FD;&#x306E;&#x305F;&#x3081;&#x306E;&#x30AA;&#x30EB;&#x30BD;&#x30ED;&#x30B0;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3042;&#x308B;

&#xC911;&#xC2EC;&#xC18C;&#xCCB4; centrosome cilium &#xD575;&#xC2EC; &#xAD6C;&#xC870; &#xC774;&#xB2E4;. &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xC911;&#xBCF5; &#xC138;&#xD3EC; &#xC8FC;&#xAE30; &#xB9C8;&#xB2E4; &#xC81C;&#xD55C; &#xC2E4;&#xD328; &#xC2EC;&#xAC01;&#xD55C; &#xACB0;&#xACFC;&#xAC00;&#xC9C0;&#xACE0; &#xD558; &#xACE0; &#xC554;&#xC5D0; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xAD00;&#xCC30; &#xD588;&#xB2E4;. &#xC758;&#xB8CC;&#xC758; &#xC911;&#xC694;&#xC131;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0; &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xD615;&#xC131;&#xC758; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC740; &#xC81C;&#xB300;&#xB85C; &#xC774;&#xD574; &#xB41C;&#xB2E4;. Asl&#xB294; &#xC774;&#xC804;&#xC5D0; centrosomal &#xB2E8;&#xBC31;&#xC9C8; centrosome &#xAE30;&#xB2A5;&#xC5D0; &#xD544;&#xC218;&#xC801;&#xC778; &#xAC83;&#xC73C;&#xB85C; &#xBCF4;&#xACE0; &#xB429;&#xB2C8;&#xB2E4;. &#xC5EC;&#xAE30; &#xC6B0;&#xB9AC;&#xAC00; mecD, asl &#xC720;&#xC804;&#xC790;&#xC758; &#xC2EC;&#xAC01;&#xD55C; &#xAE30;&#xB2A5; &#xC190;&#xC2E4; &#xB300;&#xB9BD; &#xC720;&#xC804;&#xC790; &#xC2DD;&#xBCC4; &#xACE0; &#xC911;&#xC2EC;&#xC18C;&#xCCB4;&#xC640; &#xC18D;&#xB208;&#xC379; &#xD615;&#xC131;&#xC5D0; &#xD544;&#xC694;&#xD55C; &#xC784;&#xC744; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xB9C8;&#xCC2C;&#xAC00;&#xC9C0;&#xB85C;, Cep152, &#xCC99;&#xCD94; &#xB3D9;&#xBB3C;, Asl ortholog &#xC18D;&#xB208;&#xC379; &#xD615;&#xC131;&#xC5D0; &#xD544;&#xC218;&#xC801; &#xC774;&#xBA70; &#xADF8; &#xAE30;&#xB2A5;&#xC740; &#xBD80;&#xBD84;&#xC801;&#xC73C;&#xB85C; Drosophila Asl&#xC5D0; &#xC758;&#xD574; &#xAD6C;&#xCD9C; &#xB420; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. Asl &#xC9C0;&#xC5ED;&#xD654; &#xC5F0;&#xAD6C; &#xC81C;&#xC548; &#xADF8;&#xAC83; &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xBCBD;&#xC5D0; &#xBC00;&#xC811; &#xD558; &#xAC8C; &#xC5F0;&#xAD00; &#xD558;&#xC9C0;&#xB9CC; &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xAD6C;&#xC870;&#xC5D0; &#xC18D;&#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;. Asl&#xC758; &#xACE0;&#xAC08; &#xC140;&#xC5D0; centrosomes &#xC18D; &#xBD84;&#xC11D; &#xD558; &#xC5EC; &#xC6B0;&#xB9AC;, pericentriolar &#xC18C;&#xC7AC; (PCM) &#xAE30;&#xB2A5;&#xC5D0; &#xC601;&#xD5A5;&#xC744; &#xC57D;&#xAC04; &#xB3D9;&#xC548; Asl &#xB538; &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xD615;&#xC131;&#xC744; &#xC704;&#xD574; &#xD544;&#xC218;&#xC801;&#xC785;&#xB2C8;&#xB2E4; &#xBC1C;&#xACAC;. &#xC5EC;&#xB7EC; &#xAC1C;&#xC758; centriolar &#xB9C8;&#xCEE4; mecD &#xB3CC;&#xC5F0;&#xBCC0;&#xC774;&#xC758; &#xBA85;&#xD655;&#xD55C; &#xBD80;&#xC7AC; Asl &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xC911;&#xBCF5; &#xCD08;&#xAE30;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xB098;&#xC654;&#xB2E4;.

Drosophila asterless &#xBC0F; &#xCC99;&#xCD94; cep152&#xB294; orthologs &#xC911;&#xC2EC;&#xC18C;&#xCCB4; &#xC911;&#xBCF5;&#xC5D0; &#xB300; &#xD55C; &#xD544;&#xC218;.

El centr&#xED;olo es la estructura b&#xE1;sica de centrosoma y cilio. Omisi&#xF3;n de restringir el centr&#xED;olo la duplicaci&#xF3;n de una vez por ciclo celular tiene consecuencias graves y se observa con frecuencia en el c&#xE1;ncer. A pesar de su importancia m&#xE9;dica, el mecanismo de formaci&#xF3;n centr&#xED;olo es poco conocida. El nivel del mar se hab&#xED;a informado anteriormente que es una prote&#xED;na esencial para la funci&#xF3;n centrosomal centrosoma. Aqu&#xED; identificamos MECD, una grave p&#xE9;rdida de la funci&#xF3;n alelo del gen de nivel del mar, y demostrar que se requiere para centr&#xED;olo y la formaci&#xF3;n de los cilios. Del mismo modo, Cep152, el ortholog Asl en los vertebrados, es esencial para la formaci&#xF3;n de cilios y su funci&#xF3;n puede ser parcialmente rescatado por la ASL de Drosophila. El estudio de la localizaci&#xF3;n Asl sugiere que est&#xE1; estrechamente asociado con la pared centr&#xED;olo, pero no es parte de la estructura centr&#xED;olo. Mediante el an&#xE1;lisis de la biog&#xE9;nesis de los centrosomas en c&#xE9;lulas agotadas de nivel del mar, se encontr&#xF3; que, mientras que el material pericentriolar (PCM), la funci&#xF3;n est&#xE1; levemente afectado, el ASL es esencial para la formaci&#xF3;n de su hija centr&#xED;olo. La clara ausencia de varios marcadores centriolares en mutantes del MECD sugiere que el ASL es cr&#xED;tico al inicio centr&#xED;olo duplicaci&#xF3;n.

Drosophila y vertebrados Asterless Cep152 son Orthologs esencial para la duplicaci&#xF3;n de centr&#xED;olos

Most animals have two centrioles in spermatids (the distal and proximal centrioles), but insect spermatids seem to contain only one centriole (Fuller 1993), which functionally resembles the distal centriole. Using fluorescent centriolar markers, we identified a structure near the fly distal centriole that is reminiscent of a proximal centriole (i.e., proximal centriole-like, or PCL). We show that the PCL exhibits several features of daughter centrioles. First, a single PCL forms near the proximal segment of the older centriole. Second, the centriolar proteins SAS-6, Ana1, and Bld10p/Cep135 are in the PCL. Third, PCL formation depends on SAK/PLK4 and SAS-6. Using a genetic screen for PCL defect, we identified a mutation in the gene encoding the conserved centriolar protein POC1, which is part of the daughter centriole initiation site (Kilburn et al. 2007) in Tetrahymena. We conclude that the PCL resembles an early intermediate structure of a forming centriole, which may explain why no typical centriolar structure is observed under electron microscopy. We propose that, during the evolution of insects, the proximal centriole was simplified by eliminating the later steps in centriole assembly. The PCL may provide a unique model to study early steps of centriole formation.

A proximal centriole-like structure is present in Drosophila spermatids and can serve as a model to study centriole duplication.

Centrosomes are conserved organelles that are essential for accurate cell division and cilium formation. A centrosome consists of a pair of centrioles surrounded by a protein network of pericentriolar material (PCM) that is essential for the centrosome's function. In this study, we show that Sas-4 provides a scaffold for cytoplasmic complexes (named S-CAP), which include CNN, Asl and D-PLP, proteins that are all found in the centrosomes at the vicinity of the centriole. When Sas-4 is absent, nascent procentrioles are unstable and lack PCM, and functional centrosomes are not generated. When Sas-4 is mutated, so that it cannot form S-CAP complexes, centrosomes are present but with dramatically reduced levels of PCM. Finally, purified S-CAP complexes or recombinant Sas-4 can bind centrosomes stripped of PCM, whereas recombinant CNN or Asl cannot. In summary, PCM assembly begins in the cytosol where Sas-4 provides a scaffold for pre-assembled cytoplasmic complexes before tethering of the complexes in a centrosome.

Article	Year
Nucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis. The Journal of biological chemistry\| PubMed ID: 16135518	2005
High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and Cdc20 and cause genomic instability. Cell cycle (Georgetown, Tex.)\| PubMed ID: 16222116	2005
Drosophila asterless and vertebrate Cep152 Are orthologs essential for centriole duplication. Genetics\| PubMed ID: 18854586	2008
A proximal centriole-like structure is present in Drosophila spermatids and can serve as a model to study centriole duplication. Genetics\| PubMed ID: 19293139	2009
Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome. Nature communications\| PubMed ID: 21694707	2011

Stephanie Blachon

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