BRCA1-Interacting Protein OLA1 Requires Interaction with BARD1 to Regulate Centrosome Number

Yoshino, Yuki; Qi, Huicheng; Fujita, Hiroki; Shirota, Matsuyuki; Abe, Shun; Komiyama, Yuhei; Shindo, Kazuha; Nakayama, Masahiro; Matsuzawa, Ayako; Kobayashi, Akihiro; Ogoh, Honami; Watanabe, Toshio; Ishioka, Chikashi; Chiba, Natsuko

doi:10.1158/1541-7786.mcr-18-0269

Cited by 27 publications

(37 citation statements)

References 48 publications

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“…Literature data report that FL BARD1 not in complex with BRCA1 acts as an adaptor for p53, enabling it to be targeted for ATM/ATR-directed serine-15 phosphorylation (p53Ser-15) following IR/ UV-induced DNA damage in several cell types. This phosphorylation is required for p53 apoptotic function (25,26). We observed that the depletion of FL BARD1 (in shBARD1 cells) disrupted p53Ser-15 in post-IR SKNSH and SHSY5Y cells whereas p53Ser-15 was observed in post-IR SKNSH and SHSY5Y shCTR cells ( Figure 4A).…”

Section: Fl Bard1 Functions In Regulating G2/m Cell Cycle Phase and Amentioning

confidence: 85%

“…The BARD1 RING domain is an ubiquitin ligase forming a heterodimer with BRCA1, which also harbors a RING domain. The heterodimeric complex localizes at site of DNA damage and functions in the regulation of centrosome amplification and chromosome de-condensation (25,26). Literature data report that BARD1 and BRCA1 gene knockouts have similar phenotypes demonstrating that both BARD1 and BRCA1 are essential for cell viability and maintenance of genome integrity (27,28).…”

Section: Ivyspring International Publishermentioning

confidence: 99%

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Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

et al. 2020

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BARD1 is associated with the development of high-risk neuroblastoma patients. Particularly, the expression of full length (FL) isoform, FL BARD1, correlates to high-risk neuroblastoma development and its inhibition is sufficient to induce neuroblastoma cells towards a worst phenotype. Here we have investigated the mechanisms of FL BARD1 in neuroblastoma cell lines depleted for FL BARD1 expression. We have shown that FL BARD1 expression protects the cells from spontaneous DNA damage and from damage accumulated after irradiation. We demonstrated a role for FL BARD1 as tumor suppressor to prevent unscheduled mitotic entry of DNA damaged cells and to lead to death cells that have bypassed cell cycle checkpoints. FL BARD1-depleted cells that have survived to checkpoints acquire features of aggressiveness. Overall, our results show that FL BARD1 may defend cells against cancer and prevent malignant transformation of cells.

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Section: Fl Bard1 Functions In Regulating G2/m Cell Cycle Phase and Amentioning

confidence: 85%

Section: Ivyspring International Publishermentioning

confidence: 99%

Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

et al. 2020

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“…BRCA1/BARD1 monoubiquitinates γ-tubulin at lysines K48 and K344, and the C-terminal region of BRCA1 is required for this function [10]. Suppression or overexpression of BRCA1 or BARD1 results in centrosome amplification in mammary tissue-derived cells [10,47]. Centrosome amplification induced by BRCA1 suppression is caused by premature centriole disengagement and centriole reduplication [48].…”

Section: The Brca1/bard1 Heterodimer Functions In Centrosome Regulationmentioning

confidence: 99%

The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1

Otsuka

Yoshino

et al. 2020

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Breast cancer gene 1 (BRCA1)-associated RING domain protein 1 (BARD1) forms a heterodimer with BRCA1, a tumor suppressor associated with hereditary breast and ovarian cancer. BRCA1/BARD1 functions in multiple cellular processes including DNA repair and centrosome regulation. Centrosomes are the major microtubule-organizing centers in animal cells and are critical for the formation of a bipolar mitotic spindle. BRCA1 and BARD1 localize to the centrosome during the cell cycle, and the BRCA1/BARD1 dimer ubiquitinates centrosomal proteins to regulate centrosome function. We identified Obg-like ATPase 1 (OLA1) and receptor for activated C kinase (RACK1) as BRCA1/BARD1-interating proteins that bind to BARD1 and BRCA1 and localize the centrosomes during the cell cycle. Cancer-derived variants of BRCA1, BARD1, OLA1, and RACK1 failed to interact, and aberrant expression of these proteins caused centrosome amplification due to centriole overduplication only in mammary tissue-derived cells. In S-G2 phase, the number of centrioles was higher in mammary tissue-derived cells than in cells from other tissues, suggesting their involvement in tissue-specific carcinogenesis by BRCA1 and BARD1 germline mutations. We described the function of BARD1 in centrosome regulation in cooperation with BRCA1/OLA1/RACK1, as well as the effect of their dysfunction on carcinogenesis.

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“…OLA1 can directly interact with BRCA1 and γ-tubulin by bounding to the amino-terminal of these two proteins, and this interaction is very important for the centrosomal regulation (Matsuzawa et al, 2014). And knockdown of OLA1 results in the centrosome amplification of centrosome and the disorders in microtubule aster formation (Matsuzawa et al, 2014;Yoshino et al, 2018). It is noteworthy that, BRCA1 has been shown to exert functions in oocyte meiosis, and knockdown of BRCA1 in mouse oocyte causes abnormal spindle assembly and the dysfunction of SAC (Xiong et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #1 of "OLA1 is responsible for normal spindle assembly and SAC activation in mouse oocytes (v0.1)"

2020

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Background. OLA1 is a member of the GTPase protein family, unlike other members, it possess both GTPase and ATPase activities, and can bind and hydrolyze ATP more efficiently than GTP. OLA1 participates in cell proliferation, oxidative response, protein synthesis and tumorigenesis. However, whether OLA1 is also required for oocyte meiosis is still unknown. Methods. In this study, the localization, expression, and functions of OLA1 in the mouse oocyte meiosis were examined. Immunofluorescent and confocal microscopy were used to explore the location pattern of OLA1 in the mouse oocyte. Moreover, nocodazole treatment was used to confirm the spindle-like location of OLA1 during mouse meiosis. Western blot was used to explore the expression pattern of OLA1 in the mouse oocyte. Microinjection of siRNA was used to explore the OLA1 functions in the mouse oocyte meiosis. In addition, chromosome spreading was used to investigate the spindle assembly checkpoint (SAC) activity. Results. Immunofluorescent staining showed that OLA1 evenly distributed in the cytoplasm at germinal vesicle (GV) stage. After meiosis resumption (GVBD), OLA1 co-localized with spindles, which was further identified by nocodazole treatment experiments. Knockdown of OLA1 impaired the germinal vesicle breakdown progression and finally resulted in a lower polar body extrusion rate. Immunofluorescence analysis indicated that knockdown of OLA1 led to abnormal spindle assembly, which was evidenced by multipolar spindles in OLA1-RNAi-oocytes. After 6 h post-GVBD in culture, an increased proportion of oocyte which has precociously entered into anaphase/telephase I (A/TI) was observed in OLA1knockdown oocytes, suggesting that loss of OLA1 resulted in the premature segregation of homologous chromosomes. In addition, the chromosome spread analysis suggested that OLA1 knockdown induced premature anaphase onset was due to the precocious inactivation of SAC. Taken together, we concluded that OLA1 plays important role in GVBD, spindle assembly and SAC activation maintenance in oocyte meiosis.

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BRCA1-Interacting Protein OLA1 Requires Interaction with BARD1 to Regulate Centrosome Number

Cited by 27 publications

References 48 publications

Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

The Function of BARD1 in Centrosome Regulation in Cooperation with BRCA1/OLA1/RACK1

Peer Review #1 of "OLA1 is responsible for normal spindle assembly and SAC activation in mouse oocytes (v0.1)"

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