Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing

被引：18

作者：

Liu, Yan ^{[1
,2
]}

Ferguson, Fleur M. ^{[3
,4
]}

Li, Lianbo ^{[1
,2
]}

Kuljanin, Miljan ^{[5
]}

Mills, Caitlin E. ^{[6
]}

Subramanian, Kartik ^{[6
,7
]}

Harshbarger, Wayne ^{[1
,2
]}

Gondi, Sudershan ^{[1
,2
]}

Wang, Jinhua ^{[3
,4
]}

Sorger, Peter K. ^{[6
]}

Mancias, Joseph D. ^{[5
]}

Gray, Nathanael S. ^{[3
,4
]}

Westover, Kenneth D. ^{[1
,2
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA

[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[4] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[5] Dana Farber Canc Inst, Div Radiat & Genome Stabil, Dept Radiat Oncol, Boston, MA 02115 USA

[6] Harvard Med Sch, Dept Syst Biol, Harvard Program Therapeut Sci, Lab Syst Pharmacol, Boston, MA 02115 USA

[7] Bristol Myers Squibb, 100 Binney St, Cambridge, MA 02142 USA

来源：

CELL CHEMICAL BIOLOGY | 2020年 / 27卷 / 10期

关键词：

DNA TOPOISOMERASE-II; TUMOR XENOGRAFT GROWTH; STEM-CELL MARKER; DOUBLECORTIN-LIKE; SELECTIVE INHIBITOR; HEPATOCELLULAR-CARCINOMA; PROTEIN; KINASE; EXPRESSION; SURVIVAL;

D O I：

10.1016/j.chembiol.2020.07.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Doublecortin-like kinase 1 (DCLK1) is critical for neurogenesis, but overexpression is also observed in multiple cancers and is associated with poor prognosis. Nevertheless, the function of DCLK1 in cancer, especially the context-dependent functions, are poorly understood. We present a "toolkit'' that includes the DCLK1 inhibitor DCLK1-IN-1, a complementary DCLK1-IN-1-resistant mutation G532A, and kinase dead mutants D511N and D533N, which can be used to investigate signaling pathways regulated by DCLK1. Using a cancer cell line engineered to be DCLK1 dependent for growth and cell migration, we show that this toolkit can be used to discover associations between DCLK1 kinase activity and biological processes. In particular, we show an association between DCLK1 and RNA processing, including the identification of CDK11 as a potential substrate of DCLK1 using phosphoproteomics.

引用

页码：1229 / +

页数：16

共 82 条

[21] Discovery of small molecule cancer drugs: Successes, challenges and opportunities
Hoelder, Swen
Clarke, Paul A.
Workman, Paul
[J]. MOLECULAR ONCOLOGY, 2012, 6 (02) : 155 - 176
[22] CDK11 complexes promote pre-mRNA splicing
Hu, DL
Mayeda, A
Trembley, JH
Lahti, JM
Kidd, VJ
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (10) : 8623 - 8629
[23] Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1
Ikezono, Yu
Koga, Hironori
Akiba, Jun
Abe, Mitsuhiko
Yoshida, Takafumi
Wada, Fumitaka
Nakamura, Toru
Iwamoto, Hideki
Masuda, Atsutaka
Sakaue, Takahiko
Yano, Hirohisa
Tsuruta, Osamu
Torimura, Takuji
[J]. MOLECULAR CANCER RESEARCH, 2017, 15 (06) : 744 - 752
[24] Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis
Ito, Hiromitsu
Tanaka, Shinji
Akiyama, Yoshimitsu
Shimada, Shu
Adikrisna, Rama
Matsumura, Satoshi
Aihara, Arihiro
Mitsunori, Yusuke
Ban, Daisuke
Ochiai, Takanori
Kudo, Atsushi
Arii, Shigeki
Yamaoka, Shoji
Tanabe, Minoru
[J]. PLOS ONE, 2016, 11 (01):
[25] The cellular thermal shift assay for evaluating drug target interactions in cells
Jafari, Rozbeh
Almqvist, Helena
Axelsson, Hanna
Ignatushchenko, Marina
Lundback, Thomas
Nordlund, Par
Molina, Daniel Martinez
[J]. NATURE PROTOCOLS, 2014, 9 (09) : 2100 - 2122
[26] Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis
Johnson, Janel O.
Pioro, Erik P.
Boehringer, Ashley
Chia, Ruth
Feit, Howard
Renton, Alan E.
Pliner, Hannah A.
Abramzon, Yevgeniya
Marangi, Giuseppe
Winborn, Brett J.
Gibbs, J. Raphael
Nalls, Michael A.
Morgan, Sarah
Shoai, Maryam
Hardy, John
Pittman, Alan
Orrell, Richard W.
Malaspina, Andrea
Sidle, Katie C.
Fratta, Pietro
Harms, Matthew B.
Baloh, Robert H.
Pestronk, Alan
Weihl, Conrad C.
Rogaeva, Ekaterina
Zinman, Lorne
Drory, Vivian E.
Borghero, Giuseppe
Mora, Gabriele
Calvo, Andrea
Rothstein, Jeffrey D.
Drepper, Carsten
Sendtner, Michael
Singleton, Andrew B.
Taylor, J. Paul
Cookson, Mark R.
Restagno, Gabriella
Sabatelli, Mario
Bowser, Robert
Chio, Adriano
Traynor, Bryan J.
[J]. NATURE NEUROSCIENCE, 2014, 17 (05) : 664 - +
[27] Overexpression of DCLK1 is predictive for recurrent disease in major salivary gland malignancies
Kadletz, Lorenz
Aumayr, Klaus
Heiduschka, Gregor
Schneider, Sven
Enzenhofer, Elisabeth
Lill, Claudia
[J]. EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, 2017, 274 (01) : 467 - 475
[28] Koga Hironori, 2016, Stem Cell Investig, V3, P37, DOI 10.21037/sci.2016.08.03
[29] DCLK1 Phosphorylates the Microtubule-Associated Protein MAP7D1 to Promote Axon Elongation in Cortical Neurons
Koizumi, Hiroyuki
Fujioka, Hiromi
Togashi, Kazuya
Thompson, James
Yates, John R., III
Gleeson, Joseph G.
Emoto, Kazuo
[J]. DEVELOPMENTAL NEUROBIOLOGY, 2017, 77 (04) : 493 - 510
[30] The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1
Lenart, Peter
Petronczki, Mark
Steegmaier, Martin
Di Fiore, Barbara
Lipp, Jesse J.
Hoffmann, Matthias
Rettig, Wolfgang J.
Kraut, Norbert
Peters, Jan-Michael
[J]. CURRENT BIOLOGY, 2007, 17 (04) : 304 - 315

← 1 2 3 4 5 6 7 8 9 →