Spindlin-1 docking protein (SPINÁDOC), a transcriptional repressor that binds
Spindlin-1 and masks its ability to engage the H3K4me3 activation mark [155].
SPINÁDOC associates with TCF4 in a Spindlin-1-dependent manner and dampens
Spindlin-1 coactivator activity in a TOPflash luciferase reporter assays. Furthermore,
knockdown and overexpression experiments indicated that SPINÁDOC represses the
expression of a number of Spindlin-1-regulated genes, including those encoding
ribosomal RNA and the cytokine IL1B [155].
4.3.3 Hybrid Tudor Domains (JMJ2A/KDM4A)
The hybrid Tudor domain JMJD2A/KDM4A has been poorly understood, and no
inhibitors have been published so far; thus this reader will not be further discussed
within this book chapter [156].
4.3.4 Tudor Domains that Bind Methylarginine Motifs
Tudor domains are the only protein domain family that binds methylated arginine
motifs (although individual PHD and WD40 domains also harbor this ability)
[8, 19]. Several Tudor domain-containing proteins that have been clearly shown
to participate in methylarginine-driven protein-protein interactions have been
described in the literature. These include proteins that are implicated in the regulation of splicing (SMN, important for the survival motor neuron 1 in spinal muscular
atrophy [157] and SPF30, survival of motor neuron-related-splicing factor 30 [102]),
in the regulation of gene expression (TDRD3, Tudor domain-containing protein
3 [158], and SND1, staphylococcal nuclease domain-containing protein 1 [159]),
and in a gonad-specific small RNA silencing pathway (TDRD1, TDRD6, and
TDRD9, and TDRKH [99, 160]). All of these aforementioned Tudor domain
proteins are still not fully understood, and no probes or inhibitors can be found in
the literature so far.
4.4 The MBT Domain
The MBT (malignant brain tumor) domain was originally discovered as three
repeated units in D. melanogaster gene lethal (3) malignant brain tumor [161].
Mutations in this gene correlate with tumor development in the larval brain.
The Drosophila L(3)MBT protein functions in transcriptional repression [162].
The corresponding human protein, L3MBTL1, was the first MBT protein to be
characterized structurally [163], revealing the general architecture of the MBT repeat
conserved in all other MBT structures solved to date [164]. MBT domains always
occur in two or more copies, and the arm extension of a given MBT domain packs
Methyl-Readers and Inhibitors
363
Spindlin-1 and masks its ability to engage the H3K4me3 activation mark [155].
SPINÁDOC associates with TCF4 in a Spindlin-1-dependent manner and dampens
Spindlin-1 coactivator activity in a TOPflash luciferase reporter assays. Furthermore,
knockdown and overexpression experiments indicated that SPINÁDOC represses the
expression of a number of Spindlin-1-regulated genes, including those encoding
ribosomal RNA and the cytokine IL1B [155].
4.3.3 Hybrid Tudor Domains (JMJ2A/KDM4A)
The hybrid Tudor domain JMJD2A/KDM4A has been poorly understood, and no
inhibitors have been published so far; thus this reader will not be further discussed
within this book chapter [156].
4.3.4 Tudor Domains that Bind Methylarginine Motifs
Tudor domains are the only protein domain family that binds methylated arginine
motifs (although individual PHD and WD40 domains also harbor this ability)
[8, 19]. Several Tudor domain-containing proteins that have been clearly shown
to participate in methylarginine-driven protein-protein interactions have been
described in the literature. These include proteins that are implicated in the regulation of splicing (SMN, important for the survival motor neuron 1 in spinal muscular
atrophy [157] and SPF30, survival of motor neuron-related-splicing factor 30 [102]),
in the regulation of gene expression (TDRD3, Tudor domain-containing protein
3 [158], and SND1, staphylococcal nuclease domain-containing protein 1 [159]),
and in a gonad-specific small RNA silencing pathway (TDRD1, TDRD6, and
TDRD9, and TDRKH [99, 160]). All of these aforementioned Tudor domain
proteins are still not fully understood, and no probes or inhibitors can be found in
the literature so far.
4.4 The MBT Domain
The MBT (malignant brain tumor) domain was originally discovered as three
repeated units in D. melanogaster gene lethal (3) malignant brain tumor [161].
Mutations in this gene correlate with tumor development in the larval brain.
The Drosophila L(3)MBT protein functions in transcriptional repression [162].
The corresponding human protein, L3MBTL1, was the first MBT protein to be
characterized structurally [163], revealing the general architecture of the MBT repeat
conserved in all other MBT structures solved to date [164]. MBT domains always
occur in two or more copies, and the arm extension of a given MBT domain packs
Methyl-Readers and Inhibitors
363