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@ARTICLE{Lafarga:131785,
author = {V. Lafarga and O. Tapia and S. Sharma$^*$ and R. Bengoechea
and G. Stoecklin$^*$ and M. Lafarga and M. T. Berciano},
title = {{CBP}-mediated {SMN} acetylation modulates {C}ajal body
biogenesis and the cytoplasmic targeting of {SMN}.},
journal = {Cellular and molecular life sciences},
volume = {75},
number = {3},
issn = {1420-9071},
address = {Basel},
publisher = {Birkhäuser},
reportid = {DKFZ-2018-00082},
pages = {527 - 546},
year = {2018},
note = {DKFZ-ZMBH-Allianz},
abstract = {The survival of motor neuron (SMN) protein plays an
essential role in the biogenesis of spliceosomal snRNPs and
the molecular assembly of Cajal bodies (CBs). Deletion of or
mutations in the SMN1 gene cause spinal muscular atrophy
(SMA) with degeneration and loss of motor neurons. Reduced
SMN levels in SMA lead to deficient snRNP biogenesis with
consequent splicing pathology. Here, we demonstrate that SMN
is a novel and specific target of the acetyltransferase CBP
(CREB-binding protein). Furthermore, we identify lysine (K)
119 as the main acetylation site in SMN. Importantly, SMN
acetylation enhances its cytoplasmic localization, causes
depletion of CBs, and reduces the accumulation of snRNPs in
nuclear speckles. In contrast, the acetylation-deficient
SMNK119R mutant promotes formation of CBs and a novel
category of promyelocytic leukemia (PML) bodies enriched in
this protein. Acetylation increases the half-life of SMN
protein, reduces its cytoplasmic diffusion rate and modifies
its interactome. Hence, SMN acetylation leads to its
dysfunction, which explains the ineffectiveness of HDAC
(histone deacetylases) inhibitors in SMA therapy despite
their potential to increase SMN levels.},
cin = {A200},
ddc = {570},
cid = {I:(DE-He78)A200-20160331},
pnm = {311 - Signalling pathways, cell and tumor biology
(POF3-311)},
pid = {G:(DE-HGF)POF3-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28879433},
doi = {10.1007/s00018-017-2638-2},
url = {https://inrepo02.dkfz.de/record/131785},
}