scholarly journals CEP120 interacts with CPAP and positively regulates centriole elongation

2013 ◽  
Vol 202 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Yi-Nan Lin ◽  
Chien-Ting Wu ◽  
Yu-Chih Lin ◽  
Wen-Bin Hsu ◽  
Chieh-Ju C. Tang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dimerization Domain ◽  
Interacting Protein ◽  
Centrosomal Protein ◽  
Microtubule Binding ◽  
Protein 4.1 ◽  
Centriole Duplication ◽  
Localization Domain ◽  
Microtubule Binding Domain ◽  
A Cell

Centriole duplication begins with the formation of a single procentriole next to a preexisting centriole. CPAP (centrosomal protein 4.1–associated protein) was previously reported to participate in centriole elongation. Here, we show that CEP120 is a cell cycle–regulated protein that directly interacts with CPAP and is required for centriole duplication. CEP120 levels increased gradually from early S to G2/M and decreased significantly after mitosis. Forced overexpression of either CEP120 or CPAP not only induced the assembly of overly long centrioles but also produced atypical supernumerary centrioles that grew from these long centrioles. Depletion of CEP120 inhibited CPAP-induced centriole elongation and vice versa, implying that these proteins work together to regulate centriole elongation. Furthermore, CEP120 was found to contain an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. Overexpression of a microtubule binding–defective CEP120-K76A mutant significantly suppressed the formation of elongated centrioles. Together, our results indicate that CEP120 is a CPAP-interacting protein that positively regulates centriole elongation.

scholarly journals Binding of STIL to Plk4 activates kinase activity to promote centriole assembly

2015 ◽  
Vol 209 (6) ◽  
pp. 863-878 ◽  
Author(s):  
Tyler C. Moyer ◽  
Kevin M. Clutario ◽  
Bramwell G. Lambrus ◽  
Vikas Daggubati ◽  
Andrew J. Holland
Keyword(s):  
Cell Cycle ◽  
Gene Editing ◽  
Genetic System ◽  
Genome Integrity ◽  
Chemical Genetic ◽  
Centriole Duplication ◽  
C Terminus ◽  
A Cell ◽  
Direct Binding ◽  
Centriole Assembly

Centriole duplication occurs once per cell cycle in order to maintain control of centrosome number and ensure genome integrity. Polo-like kinase 4 (Plk4) is a master regulator of centriole biogenesis, but how its activity is regulated to control centriole assembly is unclear. Here we used gene editing in human cells to create a chemical genetic system in which endogenous Plk4 can be specifically inhibited using a cell-permeable ATP analogue. Using this system, we demonstrate that STIL localization to the centriole requires continued Plk4 activity. Most importantly, we show that direct binding of STIL activates Plk4 by promoting self-phosphorylation of the activation loop of the kinase. Plk4 subsequently phosphorylates STIL to promote centriole assembly in two steps. First, Plk4 activity promotes the recruitment of STIL to the centriole. Second, Plk4 primes the direct binding of STIL to the C terminus of SAS6. Our findings uncover a molecular basis for the timing of Plk4 activation through the cell cycle–regulated accumulation of STIL.

scholarly journals Actin-dependent regulation of cilia length by the inverted formin FHDC1

2018 ◽  
Vol 29 (13) ◽  
pp. 1611-1627 ◽  
Author(s):  
Sarah J. Copeland ◽  
Andrea McRae ◽  
Giulia Guarguaglini ◽  
Laura Trinkle-Mulcahy ◽  
John W. Copeland
Keyword(s):  
Primary Cilium ◽  
Mammalian Cells ◽  
Regulatory Proteins ◽  
Interacting Protein ◽  
Microtubule Binding ◽  
Microtubule Stabilization ◽  
Microtubule Binding Domain ◽  
Cytoskeletal Dynamics ◽  
Dependent Inhibition ◽  
Cytoplasmic Microtubules

A primary cilium is found on most mammalian cells, where it acts as a cellular antenna for the reception of both mechanical and chemical signals. A variety of diseases are associated with defective ciliogenesis, reflecting the ubiquity of the function of cilia and the number of proteins required for their assembly. Proper cilia length is necessary for cilia signaling and is regulated through a poorly understood balance of assembly and disassembly rates. FHDC1 is a unique member of the formin family of cytoskeletal regulatory proteins. Overexpression of FHDC1 induces F-actin accumulation and microtubule stabilization and acetylation. We find that overexpression of FHDC1 also has profound effects on ciliogenesis; in most cells FHDC1 overexpression blocks cilia assembly, but the cilia that are present are immensely elongated. FHDC1-induced cilia growth requires the FHDC1 FH2 and microtubule-binding domain and results from F-actin–dependent inhibition of cilia disassembly. FHDC1 depletion, or treatment with a pan-formin inhibitor, inhibits cilia assembly and induces cilia resorption. Endogenous FHDC1 protein localizes to cytoplasmic microtubules converging on the base of the cilia, and we identify the subdistal appendage protein Cep170 as an FHDC1 interacting protein. Our results suggest that FHDC1 plays a role in coordinating cytoskeletal dynamics during normal cilia assembly.

scholarly journals Dynamic Recruitment of Nek2 Kinase to the Centrosome Involves Microtubules, PCM-1, and Localized Proteasomal Degradation

2005 ◽  
Vol 16 (4) ◽  
pp. 1711-1724 ◽  
Author(s):  
Rebecca S. Hames ◽  
Renarta E. Crookes ◽  
Kees R. Straatman ◽  
Andreas Merdes ◽  
Michelle J. Hayes ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Protein Degradation ◽  
Cell Cycle Progression ◽  
Proteasomal Degradation ◽  
Cycle Progression ◽  
Microtubule Binding ◽  
Multiple Processes ◽  
A Cell ◽  
Centrosomal Proteins

Centrosomes undergo dramatic changes in composition and activity during cell cycle progression. Yet mechanisms involved in recruiting centrosomal proteins are poorly understood. Nek2 is a cell cycle–regulated protein kinase required for regulation of centrosome structure at the G2/M transition. Here, we have addressed the processes involved in trafficking of Nek2 to the centrosome of human adult cells. We find that Nek2 exists in small, highly dynamic cytoplasmic particles that move to and from the centrosome. Many of these particles align along microtubules and a motif was identified in the Nek2 C-terminal noncatalytic domain that allows both microtubule binding and centrosome localization. FRAP experiments reveal that 70% of centrosomal Nek2 is rapidly turned over (t1/2 ∼ 3 s). Microtubules facilitate Nek2 trafficking to the centrosome but only over long distances. Cytoplasmic Nek2 particles colocalize in part with PCM-1 containing centriolar satellites and depletion of PCM-1 interferes with centrosomal recruitment of Nek2 and its substrate C-Nap1. Finally, we show that proteasomal degradation is necessary to allow rapid recruitment of new Nek2 molecules to the centrosome. Together, these data highlight multiple processes involved in regulating the abundance of Nek2 kinase at the centrosome including microtubule binding, the centriolar satellite component PCM-1, and localized protein degradation.

scholarly journals Septin-Dependent Assembly of a Cell Cycle-Regulatory Module in Saccharomyces cerevisiae

2000 ◽  
Vol 20 (11) ◽  
pp. 4049-4061 ◽  
Author(s):  
Mark S. Longtine ◽  
Chandra L. Theesfeld ◽  
John N. McMillan ◽  
Elizabeth Weaver ◽  
John R. Pringle ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Detectable Effect ◽  
Direct Role ◽  
Interacting Protein ◽  
Actin Organization ◽  
Cell Cycle Delay ◽  
A Cell ◽  
Morphogenesis Checkpoint ◽  
P21 Activated Kinase

ABSTRACT Saccharomyces cerevisiae septin mutants have pleiotropic defects, which include the formation of abnormally elongated buds. This bud morphology results at least in part from a cell cycle delay imposed by the Cdc28p-inhibitory kinase Swe1p. Mutations in three other genes (GIN4, encoding a kinase related to the Schizosaccharomyces pombe mitotic inducer Nim1p; CLA4, encoding a p21-activated kinase; andNAP1, encoding a Clb2p-interacting protein) also produce perturbations of septin organization associated with an Swe1p-dependent cell cycle delay. The effects of gin4, cla4, and nap1 mutations are additive, indicating that these proteins promote normal septin organization through pathways that are at least partially independent. In contrast, mutations affecting the other two Nim1p-related kinases in S. cerevisiae, Hsl1p and Kcc4p, produce no detectable effect on septin organization. However, deletion of HSL1, but not of KCC4, did produce a cell cycle delay under some conditions; this delay appears to reflect a direct role of Hsl1p in the regulation of Swe1p. As shown previously, Swe1p plays a central role in the morphogenesis checkpoint that delays the cell cycle in response to defects in bud formation. Swe1p is localized to the nucleus and to the daughter side of the mother bud neck prior to its degradation in G2/M phase. Both the neck localization of Swe1p and its degradation require Hsl1p and its binding partner Hsl7p, both of which colocalize with Swe1p at the daughter side of the neck. This localization is lost in mutants with perturbed septin organization, suggesting that the release of Hsl1p and Hsl7p from the neck may reduce their ability to inactivate Swe1p and thus contribute to the G2 delay observed in such mutants. In contrast, treatments that perturb actin organization have little effect on Hsl1p and Hsl7p localization, suggesting that such treatments must stabilize Swe1p by another mechanism. The apparent dependence of Swe1p degradation on localization of the Hsl1p-Hsl7p-Swe1p module to a site that exists only in budded cells may constitute a mechanism for deactivating the morphogenesis checkpoint when it is no longer needed (i.e., after a bud has formed).

The oncoprotein HBXIP – its functions and roles in oncogenesis

2018 ◽  
Vol 8 (2) ◽  
pp. 215-222
Author(s):  
M. Grudzinska ◽  
K. Lomperta ◽  
K. Jakubowska ◽  
P. Samocik ◽  
K. Jarząbek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Treatment Effectiveness ◽  
Malignant Tumors ◽  
Interacting Protein ◽  
Complement Dependent Cytotoxicity ◽  
Tumor Tissues ◽  
A Cell ◽  
Cancerous Cells

Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.

scholarly journals The Centrosomal Protein C-Nap1 Is Required for Cell Cycle–Regulated Centrosome Cohesion

2000 ◽  
Vol 151 (4) ◽  
pp. 837-846 ◽  
Author(s):  
Thibault Mayor ◽  
York-Dieter Stierhof ◽  
Kayoko Tanaka ◽  
Andrew M. Fry ◽  
Erich A. Nigg
Keyword(s):  
Cell Cycle ◽  
Protein C ◽  
Function Analysis ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Detailed Structure ◽  
Centrosomal Protein ◽  
Spindle Poles ◽  
Dynamic Cell ◽  
A Cell

Duplicating centrosomes are paired during interphase, but are separated at the onset of mitosis. Although the mechanisms controlling centrosome cohesion and separation are important for centrosome function throughout the cell cycle, they remain poorly understood. Recently, we have proposed that C-Nap1, a novel centrosomal protein, is part of a structure linking parental centrioles in a cell cycle–regulated manner. To test this model, we have performed a detailed structure–function analysis on C-Nap1. We demonstrate that antibody-mediated interference with C-Nap1 function causes centrosome splitting, regardless of the cell cycle phase. Splitting occurs between parental centrioles and is not dependent on the presence of an intact microtubule or microfilament network. Centrosome splitting can also be induced by overexpression of truncated C-Nap1 mutants, but not full-length protein. Antibodies raised against different domains of C-Nap1 prove that this protein dissociates from spindle poles during mitosis, but reaccumulates at centrosomes at the end of cell division. Use of the same antibodies in immunoelectron microscopy shows that C-Nap1 is confined to the proximal end domains of centrioles, indicating that a putative linker structure must contain additional proteins. We conclude that C-Nap1 is a key component of a dynamic, cell cycle–regulated structure that mediates centriole–centriole cohesion.

scholarly journals Centrobin-Centrosomal Protein 4.1-associated Protein (CPAP) Interaction Promotes CPAP Localization to the Centrioles during Centriole Duplication

2014 ◽  
Vol 289 (22) ◽  
pp. 15166-15178 ◽  
Author(s):  
Radhika Gudi ◽  
Chaozhong Zou ◽  
Jayeeta Dhar ◽  
Qingshen Gao ◽  
Chenthamarakshan Vasu
Keyword(s):  
Centrosomal Protein ◽  
Protein 4.1 ◽  
Centriole Duplication

scholarly journals APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer

2012 ◽  
Vol 31 (5) ◽  
pp. 1160-1176 ◽  
Author(s):  
Rachel Brough ◽  
Ilirjana Bajrami ◽  
Radost Vatcheva ◽  
Rachael Natrajan ◽  
Jorge S Reis-Filho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Genome Integrity ◽  
Interacting Protein ◽  
A Cell

Phosphorylation of MAP4 affects microtubule properties and cell cycle progression

2001 ◽  
Vol 114 (15) ◽  
pp. 2879-2887 ◽  
Author(s):  
Winston Chang ◽  
Dorota Gruber ◽  
Sripriya Chari ◽  
Hidefumi Kitazawa ◽  
Yuko Hamazumi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Binding Domain ◽  
Proliferating Cells ◽  
Cycle Progression ◽  
Microtubule Binding ◽  
Microtubule Binding Domain ◽  
In Cells

In human cells, MAP4, a microtubule-associated protein ubiquitously expressed in proliferating cells, has been shown to undergo in vivo phosphorylation. Two phosphorylation sites, serines 696 and 787, lie within the proline-rich region of its microtubule-binding domain. To test the hypothesis that phosphorylation at these sites influences microtubule properties or cell cycle progression, we prepared stable cell lines that inducibly express versions of MAP4 in which phosphorylation of these two serines was prevented by their replacement with alanine, lysine, or glutamate residues (AA-, KK-, or EE-MAP4). All non-phosphorylatable mutant forms of MAP4 expressed in mouse Ltk- cells were localized to MT arrays that were unremarkable in appearance. Expression of non-phosphorylatable mutants of MAP4 did not affect cell doubling time; however, expression of some mutants altered progression into or through cell division. Interactions of mutant MAP4 with MTs were examined in vitro. KK mutant MAP4 bound MTs more avidly than its wild-type counterpart, WT-MAP4. In vivo MT polymer also differed among the mutants: MTs in cells expressing the KK- and AA-MAP4 forms were more resistant to nocodazole depolymerization than those in cells expressing EE- or WT-MAP4 forms. Our results demonstrate that phosphorylation alters MAP4 properties and suggest a raison d'être for phosphorylation of the MAP4 microtubule-binding domain during cell cycle progression.

Sign in / Sign up

Export Citation Format

Share Document