RESUMO
The centrosome linker serves to hold the duplicated centrosomes together until they separate in late G2/early mitosis. Precisely how the linker is assembled remains an open question. In this study, we identify Cep44 as a novel component of the linker in human cells. Cep44 localizes to the proximal end of centrioles, including mother and daughter centrioles, and its ablation leads to loss of centrosome cohesion. Cep44 does not impinge on the stability of C-Nap1 (also known as CEP250), LRRC45 or Cep215 (also known as CDK5RAP2), and vice versa, and these proteins are independently recruited to the centrosome. Rather, Cep44 associates with rootletin and regulates its stability and localization to the centrosome. Our findings reveal a role of the previously uncharacterized protein Cep44 for centrosome cohesion and linker assembly.
Assuntos
Centrossomo , Proteínas do Citoesqueleto , Autoantígenos , Proteínas de Ciclo Celular/genética , Centríolos , Proteínas do Citoesqueleto/genética , Humanos , Mitose , Proteínas do Tecido NervosoRESUMO
During ciliogenesis, the mother centriole transforms into a basal body competent to nucleate a cilium. The mother centriole and basal body possess sub-distal appendages (SDAs) and basal feet (BF), respectively. SDAs and BF are thought to be equivalent structures. In contrast to SDA assembly, little is known about the players involved in BF assembly and its assembly order. Furthermore, the contribution of BF to ciliogenesis is not understood. Here, we found that SDAs are distinguishable from BF and that the protein NPHP5 is a novel SDA and BF component. Remarkably, NPHP5 is specifically required for BF assembly in cells able to form basal bodies but is dispensable for SDA assembly. Determination of the hierarchical assembly reveals that NPHP5 cooperates with a subset of SDA/BF proteins to organize BF. The assembly pathway of BF is similar but not identical to that of SDA. Loss of NPHP5 or a BF protein simultaneously inhibits BF assembly and primary ciliogenesis, and these phenotypes could be rescued by manipulating the expression of certain components in the BF assembly pathway. These findings define a novel role for NPHP5 in specifically regulating BF assembly, a process which is tightly coupled to primary ciliogenesis.
Assuntos
Corpos Basais/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Cílios/metabolismo , Corpos Basais/ultraestrutura , Linhagem Celular , Centríolos/metabolismo , Centríolos/ultraestrutura , Cílios/ultraestrutura , Humanos , Mapas de Interação de ProteínasRESUMO
Acetylation is among the most prevalent posttranslational modifications in cells and regulates a number of physiological processes such as gene transcription, cell metabolism, and cell signaling. Although initially discovered on nuclear histones, many non-nuclear proteins have subsequently been found to be acetylated as well. The centrosome is the major microtubule-organizing center in most metazoans. Recent proteomic data indicate that a number of proteins in this subcellular compartment are acetylated. This review gives an overview of our current knowledge on protein acetylation at the centrosome and its functional relevance in organelle biology.
Assuntos
Centrossomo/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Acetilação , Animais , Histonas/metabolismo , Humanos , ProteômicaRESUMO
The primary cilium is a cellular antenna found on the surface of many eukaryotic cells, whose main role is to sense and transduce signals that regulate growth, development, and differentiation. Although once believed to be a vestigial organelle without important function, it has become clear that defects in primary cilium are responsible for a wide variety of genetic diseases affecting many organs and tissues, including the brain, eyes, heart, kidneys, liver, and pancreas. The primary cilium is mainly present in quiescent and differentiated cells, and controls must exist to ensure that this organelle is assembled or disassembled at the right time. Although many protein components required for building the cilium have been identified, mechanistic details of how these proteins are spatially and temporally regulated and how these regulations are connected to external cues are beginning to emerge. This review article highlights the role of ubiquitination and in particular, E3 ubiquitin ligases and deubiquitinases, in the control of primary cilia assembly and disassembly.
Assuntos
Cílios/metabolismo , Ubiquitinação , Animais , Enzimas Desubiquitinantes/metabolismo , Humanos , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Viruses exploit the host cell machinery for their own profit. To evade innate immune sensing and promote viral replication, HIV type 1 (HIV-1) subverts DNA repair regulatory proteins and induces G2/M arrest. The preintegration complex of HIV-1 is known to traffic along microtubules and accumulate near the microtubule-organizing center. The centrosome is the major microtubule-organizing center in most eukaryotic cells, but precisely how HIV-1 impinges on centrosome biology remains poorly understood. We report here that the HIV-1 accessory protein viral protein R (Vpr) localized to the centrosome through binding to DCAF1, forming a complex with the ubiquitin ligase EDD-DYRK2-DDB1DCAF1 and Cep78, a resident centrosomal protein previously shown to inhibit EDD-DYRK2-DDB1DCAF1 Vpr did not affect ubiquitination of Cep78. Rather, it enhanced ubiquitination of an EDD-DYRK2-DDB1DCAF1 substrate, CP110, leading to its degradation, an effect that could be overcome by Cep78 expression. The down-regulation of CP110 and elongation of centrioles provoked by Vpr were independent of G2/M arrest. Infection of T lymphocytes with HIV-1, but not with HIV-1 lacking Vpr, promoted CP110 degradation and centriole elongation. Elongated centrioles recruited more γ-tubulin to the centrosome, resulting in increased microtubule nucleation. Our results suggest that Vpr is targeted to the centrosome where it hijacks a ubiquitin ligase, disrupting organelle homeostasis, which may contribute to HIV-1 pathogenesis.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/metabolismo , Infecções por HIV/metabolismo , HIV-1/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Centrossomo/patologia , Centrossomo/virologia , Células HEK293 , Infecções por HIV/patologia , Infecções por HIV/virologia , Células HeLa , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfoproteínas/metabolismo , Proteólise , Quinases DyrkRESUMO
Ciliogenesis is a fundamental biological process central to human health. Precisely how this process is coordinated with the cell cycle remains an open question. We report that nephrocystin-5 (NPHP5/IQCB1), a positive regulator of ciliogenesis, is a stable and low turnover protein subjected to cycles of ubiquitination and deubiquitination. NPHP5 directly binds to a deubiquitinating enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin. NPHP5 undergoes K63 ubiquitination in a cell cycle dependent manner and K48/K63 ubiquitination upon USP9X depletion or inhibition. In the G0/G1/S phase, a pool of cytoplasmic USP9X recruited to the centrosome by NPHP5 protects NPHP5 from ubiquitination, thus favouring cilia assembly. In the G2/M phase, USP9X dissociation from the centrosome allows BBS11 to K63 ubiquitinate NPHP5 which triggers protein delocalization and loss of cilia. BBS11 is a resident centrosomal protein, whereas cytoplasmic USP9X sequesters the majority of MARCH7 away from the centrosome during interphase. Depletion or inhibition of USP9X leads to an accumulation of centrosomal MARCH7 which K48 ubiquitinates NPHP5, triggering protein degradation and cilia loss. At the same time, BBS11 K63 ubiquitinates NPHP5. Our data suggest that dynamic ubiquitination and deubiquitination of NPHP5 plays a crucial role in the regulation of ciliogenesis.
Assuntos
Proteínas de Ligação a Calmodulina/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ciclo Celular , Linhagem Celular Tumoral , Centrossomo/metabolismo , Cílios/metabolismo , Células HEK293 , Humanos , Ligação ProteicaRESUMO
The centrosome plays a critical role in various cellular processes including cell division and cilia formation, and deregulation of centrosome homeostasis is a hallmark feature of many human diseases. Here, we show that centrosomal protein of 78 kDa (Cep78) localizes to mature centrioles and directly interacts with viral protein R binding protein (VprBP). Although VprBP is a component of two distinct E3 ubiquitin ligases, EDD-DYRK2-DDB1VprBP and CRL4VprBP, Cep78 binds specifically to EDD-DYRK2-DDB1VprBP and inhibits its activity. A pool of EDD-DYRK2-DDB1VprBP is active at the centrosome and mediates ubiquitination of CP110, a novel centrosomal substrate. Deregulation of Cep78 or EDD-DYRK2-DDB1VprBP perturbs CP110 ubiquitination and protein stability, thereby affecting centriole length and cilia assembly. Mechanistically, ubiquitination of CP110 entails its phosphorylation by DYRK2 and binding to VprBP Cep78 specifically impedes the transfer of ubiquitin from EDD to CP110 without affecting CP110 phosphorylation and binding to VprBP Thus, we identify Cep78 as a new player that regulates centrosome homeostasis by inhibiting the final step of the enzymatic reaction catalyzed by EDD-DYRK2-DDB1VprBP.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , Centrossomo/fisiologia , Homeostase , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Centríolos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica , Humanos , Ligação Proteica , Ubiquitinação , Quinases DyrkRESUMO
Agenesis of the corpus callosum (ACC) is a common brain malformation which can be observed either as an isolated condition or as part of numerous congenital syndromes. Therefore, cognitive and neurological involvements in patients with ACC are variable, from mild linguistic and behavioral impairments to more severe neurological deficits. To date, the underlying genetic causes of isolated ACC remains elusive and causative genes have yet to be identified. We performed exome sequencing on three acallosal siblings from the same non-consanguineous family and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously reported to cause autosomal recessive primary microcephaly. Our findings suggest a novel role for this gene in the pathogenesis of isolated ACC.
Assuntos
Agenesia do Corpo Caloso/genética , Exoma , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Adulto , Agenesia do Corpo Caloso/diagnóstico , Proteínas de Ciclo Celular , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , IrmãosRESUMO
Proper functioning of cilia, hair-like structures responsible for sensation and locomotion, requires nephrocystin-5 (NPHP5) and a multi-subunit complex called the Bardet-Biedl syndrome (BBS)ome, but their precise relationship is not understood. The BBSome is involved in the trafficking of membrane cargos to cilia. While it is known that a loss of any single subunit prevents ciliary trafficking of the BBSome and its cargos, the mechanisms underlying ciliary entry of this complex are not well characterized. Here, we report that a transition zone protein NPHP5 contains two separate BBS-binding sites and interacts with the BBSome to mediate its integrity. Depletion of NPHP5, or expression of NPHP5 mutant missing one binding site, specifically leads to dissociation of BBS2 and BBS5 from the BBSome and loss of ciliary BBS2 and BBS5 without compromising the ability of the other subunits to traffic into cilia. Depletion of Cep290, another transition zone protein that directly binds to NPHP5, causes additional dissociation of BBS8 and loss of ciliary BBS8. Furthermore, delivery of BBSome cargos, smoothened, VPAC2 and Rab8a, to the ciliary compartment is completely disabled in the absence of single BBS subunits, but is selectively impaired in the absence of NPHP5 or Cep290. These findings define a new role of NPHP5 and Cep290 in controlling integrity and ciliary trafficking of the BBSome, which in turn impinge on the delivery of ciliary cargo.
Assuntos
Antígenos de Neoplasias/metabolismo , Síndrome de Bardet-Biedl/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Cílios/metabolismo , Complexos Multiproteicos/metabolismo , Proteínas de Neoplasias/metabolismo , Antígenos de Neoplasias/genética , Síndrome de Bardet-Biedl/genética , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ciclo Celular , Cílios/genética , Proteínas do Citoesqueleto , Humanos , Complexos Multiproteicos/genética , Proteínas de Neoplasias/genética , Transporte ProteicoRESUMO
Autosomal recessive primary microcephaly (MCPH) is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas do Tecido Nervoso/genética , Animais , Proteínas de Ciclo Celular , Centrossomo/ultraestrutura , Proteínas do Citoesqueleto , Heterogeneidade Genética , Humanos , Microcefalia/genética , Microcefalia/fisiopatologia , Complexos Multiproteicos/genética , MutaçãoRESUMO
Cilia are hair-like protrusions found at the surface of most eukaryotic cells. They can be divided into two types, motile and non-motile. Motile cilia are found in a restricted number of cell types, are generally present in large numbers, and beat in a coordinated fashion to generate fluid flow or locomotion. Non-motile or primary cilia, on the other hand, are detected in many different cell types, appear once per cell, and primarily function to transmit signals from the extracellular milieu to the cell nucleus. Defects in cilia formation, function, or maintenance are known to cause a bewildering set of human diseases, or ciliopathies, typified by retinal degeneration, renal failure and cystic kidneys, obesity, liver dysfunction, and neurological disorders. A common denominator between motile and primary cilia is their structural similarity, as both types of cilia are composed of an axoneme, the ciliary backbone that is made up of microtubules emanating from a mother centriole/basal body anchored to the cell membrane, surrounded by a ciliary membrane continuous with the plasma membrane. This structural similarity is indicative of a universal mechanism of cilia assembly involving a common set of molecular players and a sophisticated, highly regulated series of molecular events. In this review, we will mainly focus on recent advances in our understanding of the regulatory mechanisms underlying cilia assembly, with special attention paid to the centriolar protein, CP110, its interacting partner Cep290, and the various downstream molecular players and events leading to intraflagellar transport (IFT), a process that mediates the bidirectional movement of protein cargos along the axoneme and that is essential for cilia formation and maintenance.
RESUMO
Mutations in the human NPHP5 gene cause retinal and renal disease, but the precise mechanism by which NPHP5 functions is not understood. We report that NPHP5 is a centriolar protein whose depletion inhibits an early step of ciliogenesis, a phenotype reminiscent of Cep290 loss and contrary to IFT88 loss. Functional dissection of NPHP5 interactions with Cep290 and CaM reveals a requirement of the former for ciliogenesis, while the latter prevents NPHP5 self-aggregation. Disease-causing mutations lead to truncated products unable to bind Cep290 and localize to centrosomes, thereby compromising cilia formation. In contrast, a modifier mutation cripples CaM binding but has no overt effect on ciliogenesis. Drugs that antagonize negative regulators of the ciliogenic pathway can rescue ciliogenesis in cells depleted of NPHP5, with response profiles similar to those of Cep290- but not IFT88-depleted cells. Our results uncover the underlying molecular basis of disease and provide novel insights into mitigating NPHP5 deficiency.
Assuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Cílios/metabolismo , Doenças Renais Císticas/metabolismo , Amaurose Congênita de Leber/metabolismo , Mutação , Proteínas de Neoplasias/metabolismo , Atrofias Ópticas Hereditárias/metabolismo , Antígenos de Neoplasias/genética , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ciclo Celular , Linhagem Celular , Centríolos/genética , Centríolos/metabolismo , Ciliopatias , Proteínas do Citoesqueleto , Humanos , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologia , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Proteínas de Neoplasias/genética , Atrofias Ópticas Hereditárias/genética , Atrofias Ópticas Hereditárias/patologia , Ligação Proteica , Transporte ProteicoRESUMO
Merkel cell carcinoma is an uncommon primary neuroendocrine neoplasm of the skin that may exhibit divergent differentiation. However, rhabdomyosarcomatous differentiation has only been rarely described and takes the form of isolated rhabdomyoblasts. We describe a case of cutaneous Merkel cell carcinoma with biphasic morphology imparted by discrete patches of embryonal rhabdomyosarcoma-like spindle cells alternating with islands of neuroendocrine small round cells, justifying a designation of "Merkel cell carcinosarcoma." The former component showed positive immunostaining for desmin and myogenin; and the later component, pan-cytokeratin, cytokeratin 20, synaptophysin, and chromogranin. The patient was an elderly man who presented with a temporal skin mass, and the biphasic morphology was evident in the recurrence and metastasis that developed 2 months after incomplete excision of the skin lesion.
Assuntos
Carcinoma de Célula de Merkel/patologia , Rabdomiossarcoma Embrionário/patologia , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Carcinoma de Célula de Merkel/cirurgia , Evolução Fatal , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/cirurgia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/cirurgiaRESUMO
We have identified a protein, Kif24, that shares homology with the kinesin-13 subfamily of motor proteins and specifically interacts with CP110 and Cep97, centrosomal proteins that play a role in regulating centriolar length and ciliogenesis. Kif24 preferentially localizes to mother centrioles. Loss of Kif24 from cycling cells resulted in aberrant cilia assembly but did not promote growth of abnormally long centrioles, unlike CP110 and Cep97 depletion. We found that loss of Kif24 leads to the disappearance of CP110 from mother centrioles, specifically in cycling cells able to form cilia. Kif24 is able to bind and depolymerize microtubules in vitro. Remarkably, ectopically expressed Kif24 specifically remodels centriolar microtubules without significantly altering cytoplasmic microtubules. Thus, our studies have identified a centriolar kinesin that specifically remodels a subset of microtubules, thereby regulating cilia assembly. These studies also suggest mechanistic differences between the regulation of microtubule elongation associated with centrioles and cilia.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Cílios/metabolismo , Cinesinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Fosfoproteínas/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Humanos , Cinesinas/química , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
Centrosomes duplicate only once per cell cycle, but the controls that govern this process are largely unknown. We have identified Cep76, a centriolar protein that interacts with CP110. Cep76 is expressed at low levels in G1 and is induced in S and G2 phase, during which point centrioles have already commenced duplication. Interestingly, depletion of Cep76 drives the accumulation of centriolar intermediates in certain types of cancer cells. Enforced Cep76 expression specifically inhibits centriole amplification in cells undergoing multiple rounds of duplication without preventing the formation of extra procentrioles from a parental template. Furthermore, elevated levels of Cep76 do not affect normal centriole duplication. Thus, Cep76 helps limit duplication to once per cell cycle. Our findings also point to mechanistic differences between normal duplication and aberrant centriole amplification, as well as distinctions between diverse modes of amplification.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Ciclo Celular , Centríolos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Fase G2 , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Fase SAssuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Regulação Neoplásica da Expressão Gênica , Hibridização in Situ Fluorescente , Receptor ErbB-2/genética , Biópsia por Agulha , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Estudos de Coortes , Feminino , Hong Kong , Humanos , Imuno-Histoquímica , Sensibilidade e EspecificidadeRESUMO
Primary cilia are nonmotile organelles implicated in signaling and sensory functions. Understanding how primary cilia assemble could shed light on the many human diseases caused by mutations in ciliary proteins. The centrosomal protein CP110 is known to suppress ciliogenesis through an unknown mechanism. Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease--in a discrete complex separable from other CP110 complexes involved in regulating the centrosome cycle. Ablation of CEP290 prevents ciliogenesis without affecting centrosome function or cell-cycle progression. Interaction with CEP290 is absolutely required for the ability of CP110 to suppress primary cilia formation. Furthermore, CEP290 and CP110 interact with Rab8a, a small GTPase required for cilia assembly. Depletion of CEP290 interferes with localization of Rab8a to centrosomes and cilia. Our results suggest that CEP290 cooperates with Rab8a to promote ciliogenesis and that this function is antagonized by CP110.
Assuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cílios/metabolismo , Cílios/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/metabolismo , Animais , Linhagem Celular , Centrossomo/metabolismo , Proteínas do Citoesqueleto , Humanos , Camundongos , Modelos Biológicos , Proteínas Mutantes/metabolismo , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Transporte Proteico , Interferência de RNA , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
We report 3 cases of a previously uncharacterized form of histiocytosis presenting in early infancy and showing ALK immunoreactivity. The patients presented with pallor, massive hepatosplenomegaly, anemia, and thrombocytopenia. Liver biopsy showed infiltration of the sinusoids by large histiocytes with markedly folded nuclei, fine chromatin, small nucleoli, and voluminous lightly eosinophilic cytoplasm that sometimes was vacuolated or contained phagocytosed blood cells. One patient developed cutaneous infiltrates that morphologically resembled juvenile xanthogranuloma. The histiocytes were immunoreactive for histiocytic markers (CD68, CD163, lysozyme), S100 protein, ALK (membranous and cytoplasmic pattern), and dendritic cell markers (fascin, factor XIIIa), but not CD1a and langerin. One case successfully analyzed by molecular techniques revealed TPM3-ALK fusion. Thus the spectrum of diseases exhibiting ALK translocation should be expanded to include ALK(+) histiocytosis. The disease in the 3 patients (2 having been given chemotherapy) resolved slowly over many months.
Assuntos
Receptores de Activinas Tipo II/metabolismo , Histiócitos/patologia , Histiocitose/patologia , Biópsia , Proliferação de Células , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Transporte Proteico , Pele/patologiaRESUMO
Sgo1 plays a key role in protecting sister chromatid cohesion during mitosis. In this issue of Developmental Cell, Wang et al. describe a shorter splice variant of Sgo1 (sSgo1) that functions specifically in centriole cohesion. sSgo1 may be the "glue" that holds paired centrioles together in an engaged state before their disengagement in late mitosis.