SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC to facilitate NotchIC function

被引:210
作者
Zhou, SF
Fujimuro, M
Hsieh, JJD
Chen, L
Miyamoto, A
Weinmaster, G
Hayward, SD
机构
[1] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[2] Johns Hopkins Sch Med, Ctr Oncol, Baltimore, MD 21205 USA
[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
关键词
D O I
10.1128/MCB.20.7.2400-2410.2000
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
Notch proteins are transmembrane receptors that mediate intercell communication and direct individual cell fate decisions. The activated intracellular form of Notch, NotchIC, translocates to the nucleus, where it targets the DNA binding protein CBF1. CBF1 mediates transcriptional repression through the recruitment of an SMRT-histone deacetylase-containing corepressor complex. We have examined the mechanism whereby NotchIC overcomes CBF1-mediated transcriptional repression. We identified SKIP (Ski-interacting protein) as a CBF1 binding protein in a yeast two-hybrid screen. Both CBF1 and SKIP are highly conserved evolutionarily, and the SKIP-CBF1 interaction is also conserved in assays using the Caenorhabditis elegans and Drosophila melanogaster SKIP homologs. Protein-protein interaction assays demonstrated interaction between SKIP and the corepressor SMRT. More surprisingly, SKIP also interacted with NotchIC. The SMRT and NotchIC interactions were mutually exclusive. In competition binding experiments SMRT displaced NotchIC from CBF1 and from SKIP. Contact with SKIP is required for biological activity of NotchIC. A mutation in the fourth ankyrin repeat that abolished Notch signal transduction did not affect interaction with CBF1 but abolished interaction with SKIP. Further, NotchIC was unable to block muscle cell differentiation in myoblasts expressing antisense SKIP. The results suggest a model in which NotchIC activates responsive promoters by competing with the SMRT-corepressor complex for contacts on both CBF1 and SKIP.
引用
收藏
页码:2400 / 2410
页数:11
相关论文
共 63 条
[51]   CONTROL OF CELL FATE IN C-ELEGANS BY A GLP-1 PEPTIDE CONSISTING PRIMARILY OF ANKYRIN REPEATS [J].
ROEHL, H ;
KIMBLE, J .
NATURE, 1993, 364 (6438) :632-635
[52]   Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma [J].
Rohn, JL ;
Lauring, AS ;
Linenberger, ML ;
Overbaugh, J .
JOURNAL OF VIROLOGY, 1996, 70 (11) :8071-8080
[53]   Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain [J].
Schroeter, EH ;
Kisslinger, JA ;
Kopan, R .
NATURE, 1998, 393 (6683) :382-386
[54]  
Shawber C, 1996, DEVELOPMENT, V122, P3765
[55]   Nuclear access and action of notch in vivo [J].
Struhl, G ;
Adachi, A .
CELL, 1998, 93 (04) :649-660
[56]   INTRINSIC ACTIVITY OF THE LIN-12 AND NOTCH INTRACELLULAR DOMAINS IN-VIVO [J].
STRUHL, G ;
FITZGERALD, K ;
GREENWALD, I .
CELL, 1993, 74 (02) :331-345
[57]   Presenilin is required for activity and nuclear access of Notch in Drosophila [J].
Struhl, G ;
Greenwald, I .
NATURE, 1999, 398 (6727) :522-525
[58]   RECOGNITION SEQUENCE OF A HIGHLY CONSERVED DNA-BINDING PROTEIN RBP-JKAPPA [J].
TUN, T ;
HAMAGUCHI, Y ;
MATSUNAMI, N ;
FURUKAWA, T ;
HONJO, T ;
KAWAICHI, M .
NUCLEIC ACIDS RESEARCH, 1994, 22 (06) :965-971
[59]   The ins and outs of Notch signaling [J].
Weinmaster, G .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1997, 9 (02) :91-102
[60]   Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants [J].
Ye, YH ;
Lukinova, N ;
Fortini, ME .
NATURE, 1999, 398 (6727) :525-529