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      • The N-terminal domain of DDA3 regulates the spindle-association of the microtubule depolymerase Kif2a and controls the mitotic function of DDA3.

        Jang, Chang-Young,Fang, Guowei Landes Bioscience 2009 Cell cycle Vol.8 No.19

        <P>DDA3 is a microtubule-associated protein that controls chromosome congression and segregation by regulating the dynamics of the mitotic spindle. Depletion of DDA3 alters spindle structure, generates unaligned chromosomes at metaphase, and delays the mitotic progression. DDA3 interacts with the microtubule depolymerase Kif2a and controls the association of Kif2a to the mitotic spindle and the dynamic turnover of microtubules in the spindle. To understand the function and regulation of DDA3, we analyzed its domain structure and found that the C-terminal domain of DDA3 directly binds to microtubules in vitro and associates with the mitotic spindle in vivo. The N-terminal domain of DDA3 does not interact with microtubules, but acts dominant negatively over the wild-type protein. Ectopic expression of this domain prevents the endogenous DDA3 from association with the spindle and results in a high frequency of unaligned chromosomes in metaphase cells, a phenotype similar to that in metaphase cells depleted of DDA3. Mechanistically, expression of N-terminal DDA3 reduces the amount of spindle-associated Kif2a and increases the spindle microtubule density, pheno-copying those in DDA3-depleted cells. We conclude that DDA3 has a distinct domain structure. The C-terminal domain confers its ability to associate with the mitotic spindle, while the regulatory N-terminal domain controls the microtubule-binding by the C-terminal domain and determines the cellular activity of the DDA3 protein.</P>

      • KCI등재

        Mechanism, Function and Regulation of Microtubule-Dependent Microtubule Amplification in Mitosis

        Hui Zhu,Kayleen Fang,Guowei Fang 한국분자세포생물학회 2009 Molecules and cells Vol.27 No.1

        Mitotic spindle mediates the segregation of chromosomes in the cell cycle and the proper function of the spindle is crucial to the high fidelity of chromosome segregation and to the stability of the genome. Nucleation of microtubules (MTs) from centrosomes and chromatin represents two well-characterized pathways essential for the assembly of a dynamic spindle in mitosis. Recently, we identified a third MT nucleation pathway, in which existing MTs in the spindle act as a template to promote the nucleation and polymerization of MTs, thereby efficiently amplifying MTs in the spindle. We will review here our current understanding on the molecular mechanism, the physiological function and the cell-cycle regulation of MT amplification.

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        Surgical Treatment for 11 Cases of Penile Verrucous Carcinoma

        Sun Chuanyu,Xu Ke,Zheng Jie,Xia Guowei,Fang Zujun,Ding Qiang 대한피부과학회 2011 Annals of Dermatology Vol.23 No.-

        Penile verrucous carcinoma is a rare, well-differentiated and low-grade tumor. The surgeons are deficiently aware about the biological behavior and the clinicopathological characteristic of this disease, which raises difficulties during the treatment. In our present study, the clinical and pathological data of 11 patients with penile verrucous carcinoma, aged between 49 to 85 years was retrospectively analyzed. The tumors exhibited exophytic, papillary, caulifower-like or verrucose lesions of great dimensions measuring between 2to 10 cm on the penises. The tumors were located at glans in 6 cases, invaded the coronoid sulcus in 4 cases and invaded the shaft of the penis in 1 case. Eight cases underwent partial penectomy, while the other 3 were treated with local excision. The diagnosis of penile verrucous carcinoma was confirmed by histopathologic examination of the specimens with the negative surgical margins in all the cases. Within the period of 12 to 60 months of follow-up, all the patients were disease-free with no case of recurrence and metastasis. The novel knowledge and experience of the treatment of penile verrucous carcinoma will be a useful clinical guide for surgeons in the future. (Ann Dermatol 23(S3) S346∼S349,2011)

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