KRAB domain of ZFP568 disrupts TRIM28-mediated abnormal interactions in cancer cells.

NAR Cancer
Janani KumarXiaodong Cheng

Abstract

Interactions of KRAB (Krüppel-associated box)-associated protein KAP1 [also known as TRIM28 (tripartite motif containing protein 28)] with DNA-binding KRAB zinc finger (KRAB-ZF) proteins silence many transposable elements during embryogenesis. However, in some cancers, TRIM28 is upregulated and interacts with different partners, many of which are transcription regulators such as EZH2 in MCF7 cells, to form abnormal repressive or activating complexes that lead to misregulation of genes. We ask whether a KRAB domain-the TRIM28 interaction domain present in native binding partners of TRIM28 that mediate repression of transposable elements-could be used as a tool molecule to disrupt aberrant TRIM28 complexes. Expression of KRAB domain containing fragments from a KRAB-ZF protein (ZFP568) in MCF7 cells, without the DNA-binding zinc fingers, inhibited TRIM28-EZH2 interactions and caused degradation of both TRIM28 and EZH2 proteins as well as other components of the EZH2-associated polycomb repressor 2 complex. In consequence, the product of EZH2 enzymatic activity, trimethylation of histone H3 lysine 27 level, was significantly reduced. The expression of a synthetic KRAB domain significantly inhibits the growth of breast cancer cells ...Continue Reading

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Citations

Dec 18, 2020·International Journal of Molecular Sciences·Jun Wang, Gang Greg Wang
Jan 23, 2021·Chembiochem : a European Journal of Chemical Biology·Francesca D'AmicoMonique P C Mulder

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Datasets Mentioned

BETA
GSE146769

Methods Mentioned

BETA
X-ray
protein
RNA-seq
transfection
fluorescence-activated cell sorter
FACS
size-exclusion chromatography
size-exclusion
two
pull-down

Software Mentioned

FACS DIVA
ImageJ
Ingenuity Pathway Analysis
QIAGEN

Related Concepts