AnthonyKi Lui

Publications

• 5.33

  Impact points

  CHCM1/CHCHD6, Novel Mitochondrial Protein Linked to Regulation of Mitofilin and Mitochondrial Cristae Morphology.

  Jie An, Jingxue Shi, Qin He, Ki Lui, Yuxin Liu, Ying Huang, M Saeed Sheikh

  The Journal of biological chemistry. 03/2012; 287(10):7411-26.

  The structural integrity of mitochondrial cristae is crucial for mitochondrial functions; however, the molecular events controlling the structural integrity and biogenesis of mitochondrial cristae remain to be fully elucidated. Here, we report the functional characterization of a novel mitochondrial... [more] The structural integrity of mitochondrial cristae is crucial for mitochondrial functions; however, the molecular events controlling the structural integrity and biogenesis of mitochondrial cristae remain to be fully elucidated. Here, we report the functional characterization of a novel mitochondrial protein named CHCM1 (coiled coil helix cristae morphology 1)/CHCHD6. CHCM1/CHCHD6 harbors a coiled coil helix-coiled coil helix domain at its C-terminal end and predominantly localizes to mitochondrial inner membrane. CHCM1/CHCHD6 knockdown causes severe defects in mitochondrial cristae morphology. The mitochondrial cristae in CHCM1/CHCHD6-deficient cells become hollow with loss of structural definitions and reduction in electron-dense matrix. CHCM1/CHCHD6 depletion also leads to reductions in cell growth, ATP production, and oxygen consumption. CHCM1/CHCHD6 through its C-terminal end strongly and directly interacts with the mitochondrial inner membrane protein mitofilin, which is known to also control mitochondrial cristae morphology. CHCM1/CHCHD6 also interacts with other mitofilin-associated proteins, including DISC1 and CHCHD3. Knockdown of CHCM1/CHCHD6 reduces mitofilin protein levels; conversely, mitofilin knockdown leads to reduction in CHCM1 levels, suggesting coordinate regulation between these proteins. Our results further indicate that genotoxic anticancer drugs that induce DNA damage down-regulate CHCM1/CHCHD6 expression in multiple human cancer cells, whereas mitochondrial respiratory chain inhibitors do not affect CHCM1/CHCHD6 levels. CHCM1/CHCHD6 knockdown in human cancer cells enhances chemosensitivity to genotoxic anticancer drugs, whereas its overexpression increases resistance. Collectively, our results indicate that CHCM1/CHCHD6 is linked to regulation of mitochondrial cristae morphology, cell growth, ATP production, and oxygen consumption and highlight its potential as a possible target for cancer therapeutics.
• 5.33

  Impact points

  Identification and characterization of RBEL1 subfamily of GTPases in the Ras superfamily involved in cell growth regulation.

  JoAnne Montalbano, Ki Lui, M Saeed Sheikh, Ying Huang

  The Journal of biological chemistry. 06/2009;

  Recently, we reported the identification of a novel gene named RBEL1 (Rab-like protein 1) and characterized its two encoded isoforms, RBEL1A and RBEL1B, that function as novel GTPases of Ras superfamily. Here we report the identification of two additional splice variants of RBEL1 that we have named ... [more] Recently, we reported the identification of a novel gene named RBEL1 (Rab-like protein 1) and characterized its two encoded isoforms, RBEL1A and RBEL1B, that function as novel GTPases of Ras superfamily. Here we report the identification of two additional splice variants of RBEL1 that we have named RBEL1C and D. All four RBEL1 isoforms (A, B, C and D) have identical N-termini harboring the Rab-like GTPase domains but contain variable C-termini. Although all isoforms can be detected in both cytoplasm and nucleus, RBEL1A is predominantly cytoplasmic while RBEL1B is mostly nuclear. RBEL1C and D, by contrast, are evenly distributed between the cytoplasm and nucleus. Furthermore, all four RBEL1 proteins are also capable of associating with cellular membrane. The RBEL1 proteins also exhibit a unique nucleotide binding potential and while the larger A and B isoforms are mainly GTP-bound, the smaller C and D variants bind to both GTP and GDP. Furthermore, a regulatory region at amino acid position 236-302 immediately adjacent to the GTP-binding domain is important for GTPbinding potential of RBEL1A, as deletion of this region converts RBEL1A from predominantly GTP-bound to GDP-bound. RBEL1 knockdown via RNAi results in marked cell growth suppression that is associated with morphological and biochemical features of apoptosis as well as inhibition of extracellular signal regulated kinase (ERK) phosphorylation. Taken together, our results indicate that RBEL1 proteins are linked to cell growth and survival, and possess unique biochemical, cellular and functional characteristics, and therefore, appear to form a novel subfamily of GTPases within the Ras superfamily.

• RanGTPase: A Key Regulator of Nucleocytoplasmic Trafficking.

  Ki Lui, Ying Huang

  Molecular and cellular pharmacology. 01/2009; 1(3):148-156.

  RanGTPase belongs to the Ras superfamily of small GTPases. It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase is known to regulate nucleocytoplasmic trafficking as well as mitotic spindle and nuclear envelope formation. Ran-directed nucleo... [more] RanGTPase belongs to the Ras superfamily of small GTPases. It possesses a distinctive acidic C-terminal DEDDDL motif and predominantly localizes to the nucleus. RanGTPase is known to regulate nucleocytoplasmic trafficking as well as mitotic spindle and nuclear envelope formation. Ran-directed nucleocytoplasmic trafficking is an energy-dependent directional process that also depends on nuclear import or export signals. Ran-directed nucleocytoplasmic trafficking is also facilitated by several cellular components, including RanGTPase, karyopherins, NTF2 and nucleoporins. GTP-bound Ran is asymmetrically distributed in the nucleus, while GDP-bound Ran is predominantly cytoplasmic. Controlled by RanGEF and RanGAP, RanGTPase cycles between the GDP- and GTP-bound states enabling it to shuttle cargoes in an accurate spatial and temporal manner. RanGTPase plays a role in the nuclear import in such a way that GTP-bound Ran dissociates importin:cargo complex in the nucleus and recycles importin back to cytoplasm. Likewise, RanGTPase plays a role in the nuclear export in such a way that nuclear GTP-bound Ran triggers the aggregation of Ran:exportin:cargo trimeric complex which is then transported to cytoplasm while hydrolysis of RanGTP to RanGDP releases the export cargoes in cytoplasm. RanGTPase has been reported to be essential for cell viability and its over-expression is linked to tumorigenesis. Thus, RanGTPase plays a crucial role in regulating key cellular events and alterations in its expression may lead to cancer development and/or progression.

• Characterization of the weak estrogen receptor alpha agonistic activity of exemestane.

  Masri S, Lui K, Phung S, Ye J, Zhou D, Wang X, Chen S.

  Breast Cancer Res Treat. Epub ahead of print.

• The molecular basis of the interaction between the praline-rich SH3-binding motif of PNRC and estrogen receptor alpha.

  Dujin Zhou, Jing Jing Ye, Yuping Li, K. Lui, Shiuan Chen

  Nucleic Acids Res. 20:5974-86.

• Molecular Cloning and Functional Study of Rat Estrogen Receptor-Related in rat Prostatic cells.

  (5) K. Lui, Yu Huang, HL. Choi, Shan Yu, K.B. Wong, Shiuan Chen, Franky L. Chan

  Prostate. 15:1600-19..

• White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice.

  Adams LS, Phung S, Wu X, Lui K, Chen S.

  Nutr Cancer. 60:744-56.

• MCF-7aro/ERE, a novel cell line for rapid screening of aromatase inhibitors, ERalpha ligands and ERRalpha ligands

  Lui K, Tamura T, Mori T, Zhou D, Chen S.

  Biochem Pharmacol.

• Expression Study of Estrogen Receptor-related Receptors and Steroid Hormone Receptors in Human Prostatic Cells.

  (6) C.P. Cheung, Lung-Wai Chan, K. Lui, Uwe Borgmeyer, Shiuan Chen, Franky L. Chan

  Hormonal Carcinogensis. IV:501-507.

• An Expression Study of Three Secretory Proteins (Prostatic Secretory Protein of 94 Amino Acids, Probasin, and Seminal Vesicle Secretion II) in Dysplastic and Neoplastic Rat Prostates.

  (7) Joseph Kwong, Peter S.F. Chan, K. Lui, J.W. Xuan, Shuk-Mei Ho, Y.C. Wong, Franky L. Chan

  Prostate. 56:81-97.