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
收藏
页码：1229 / +
页数：16
相关论文
共 82 条
  • [1] CDK11 Loss Induces Cell Cycle Dysfunction and Death of BRAF and NRAS Melanoma Cells
    Ahmed, Rehana L.
    Shaughnessy, Daniel P.
    Knutson, Todd P.
    Vogel, Rachel, I
    Ahmed, Khalil
    Kren, Betsy T.
    Trembley, Janeen H.
    [J]. PHARMACEUTICALS, 2019, 12 (02)
  • [2] Austin CA, 1998, BIOESSAYS, V20, P215, DOI 10.1002/(SICI)1521-1878(199803)20:3<215::AID-BIES5>3.0.CO
  • [3] 2-Q
  • [4] DCLK1 Marks a Morphologically Distinct Subpopulation of Cells With Stem Cell Properties in Preinvasive Pancreatic Cancer
    Bailey, Jennifer M.
    Alsina, Janivette
    Rasheed, Zeshaan A.
    McAllister, Florencia M.
    Fu, Ya-Yuan
    Plentz, Ruben
    Zhang, Hao
    Pasricha, Pankaj J.
    Bardeesy, Nabeel
    Matsui, William
    Maitra, Anirban
    Leach, Steven D.
    [J]. GASTROENTEROLOGY, 2014, 146 (01) : 245 - 256
  • [5] Comprehensive molecular characterization of gastric adenocarcinoma
    Bass, Adam J.
    Thorsson, Vesteinn
    Shmulevich, Ilya
    Reynolds, Sheila M.
    Miller, Michael
    Bernard, Brady
    Hinoue, Toshinori
    Laird, Peter W.
    Curtis, Christina
    Shen, Hui
    Weisenberger, Daniel J.
    Schultz, Nikolaus
    Shen, Ronglai
    Weinhold, Nils
    Keiser, David P.
    Bowlby, Reanne
    Sipahimalani, Payal
    Cherniack, Andrew D.
    Getz, Gad
    Liu, Yingchun
    Noble, Michael S.
    Pedamallu, Chandra
    Sougnez, Carrie
    Taylor-Weiner, Amaro
    Akbani, Rehan
    Lee, Ju-Seog
    Liu, Wenbin
    Mills, Gordon B.
    Yang, Da
    Zhang, Wei
    Pantazi, Angeliki
    Parfenov, Michael
    Gulley, Margaret
    Piazuelo, M. Blanca
    Schneider, Barbara G.
    Kim, Jihun
    Boussioutas, Alex
    Sheth, Margi
    Demchok, John A.
    Rabkin, Charles S.
    Willis, Joseph E.
    Ng, Sam
    Garman, Katherine
    Beer, David G.
    Pennathur, Arjun
    Raphael, Benjamin J.
    Wu, Hsin-Ta
    Odze, Robert
    Kim, Hark K.
    Bowen, Jay
    [J]. NATURE, 2014, 513 (7517) : 202 - 209
  • [6] POLARITY AS A CRITERION IN PROTEIN DESIGN
    BAUMANN, G
    FROMMEL, C
    SANDER, C
    [J]. PROTEIN ENGINEERING, 1989, 2 (05): : 329 - 334
  • [7] Compensatory metabolic networks in pancreatic cancers upon perturbation of glutamine metabolism
    Biancur, Douglas E.
    Paulo, Joao A.
    Malachowska, Beata
    Del Rey, Maria Quiles
    Sousa, Cristovao M.
    Wang, Xiaoxu
    Sohn, Albert S. W.
    Chu, Gerald C.
    Gygi, Steven P.
    Harper, J. Wade
    Fendler, Wojciech
    Mancias, Joseph D.
    Kimmelman, Alec C.
    [J]. NATURE COMMUNICATIONS, 2017, 8
  • [8] Chandrakesan P., 2016, J. Carcinog. Mutagen, V7, P257, DOI DOI 10.4172/2157-2518.1000257
  • [9] Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells
    Chandrakesan, Parthasarathy
    Yao, Jiannan
    Qu, Dongfeng
    May, Randal
    Weygant, Nathaniel
    Ge, Yang
    Ali, Naushad
    Sureban, Sripathi M.
    Gude, Modhi
    Vega, Kenneth
    Bannerman-Menson, Eddie
    Xia, Lijun
    Bronze, Michael
    An, Guangyu
    Houchen, Courtney W.
    [J]. MOLECULAR CANCER, 2017, 16
  • [10] Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal
    Chandrakesan, Parthasarathy
    May, Randal
    Qu, Dongfeng
    Weygant, Nathaniel
    Taylor, Vivian E.
    Li, James D.
    Ali, Naushad
    Sureban, Sripathi M.
    Qante, Michael
    Wang, Timothy C.
    Bronze, Michael S.
    Houchen, Courtney W.
    [J]. ONCOTARGET, 2015, 6 (31) : 30876 - 30886
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