Nuclear bodies (also known as nuclear domains, or nuclear dots) are membraneless structures found in the
cell nuclei of
eukaryoticcells.[1] Nuclear bodies include
Cajal bodies, the
nucleolus, and
promyelocytic leukemia protein (PML) nuclear bodies (also called PML oncogenic dots).[2] Nuclear bodies also include ND10s. ND stands for nuclear domain, and 10 refers to the number of dots seen.[3]
Nuclear bodies were first seen as prominent interchromatin structures in the nuclei of malignant or hyperstimulated animal cells[4][5] identified using
anti-sp100 autoantibodies from
primary biliary cirrhosis and subsequently the promyelocytic leukemia (PML) factor, but appear also to be elevated in many autoimmune and cancerous diseases.[6] Nuclear dots are metabolically stable and resistant to nuclease digestion and salt extraction.[7]
A nuclear body subtype is a
clastosome suggested to be a site of protein degradation.[8]
Structure
Simple nuclear bodies (types I and II) and the shells of complex nuclear bodies (types III, IVa and V) consist of a non-chromatinic fibrillar material which is most likely proteinaceous.[9] That nuclear bodies co-isolated with the nuclear matrix, and were linked to the fibrogranular nuclear matrix component by projections from the surface of the nuclear bodies.[9] The primary components of the nuclear dots are the proteins sp100 nuclear antigen, LYSP100(a homolog of sp100),[10]ISG20,[11]PML antigen,
NDP55 and 53kDa protein associated with the nuclear matrix.[12] Other proteins, such as PIC1/SUMO-1, which are associated with
nuclear pore complex also associate with nuclear dots.[13] The proteins can reorganize in the nucleus, by increasing number of dispersion in response to different stress (stimulation or heat shock, respectively).[14]
Function
One of the nuclear body proteins appears to be involved in transcriptional active regions.[15] Expression of PML antigen and
sp100 is responsive to interferons. Sp100 seems to have transcriptional transactivating properties. PML protein was reported to suppress growth and transformation,[5] and specifically inhibits the infection of vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus,[16] but not other types of viruses. The
SUMO-1ubiquitin like protein is responsible for modifying PML protein such that it is targeted to dots.[17] whereas overexpression of PML results in programmed cell death.[18]
One hypothesized function of the dots is as a 'nuclear dump' or 'storage depot'.
[19] The nuclear bodies may not all perform the same function.
Sp140 associates with certain bodies and appears to be involved in transcriptional activation.[20]
ND10 nuclear bodies have been shown to play a major role in
chromatin regulation.[21]
Pathology
These, or similar, bodies have been found increased in the presence of lymphoid cancers[22][23] and
SLE (lupus).[24] They are also observed at higher frequencies in
subacute sclerosing panencephalitis; in this instance, antibodies to
measles show expression in and localization to the nuclear bodies.[25]
In
promyelocytic leukemia (PML), the oncogenic PML-
retinoic acid receptor alpha (RARalpha) chimera disrupts the normal concentration of PML in nuclear bodies. Administration of
arsenic trioxide (As2O3) plus
all-trans retinoic acid (Tretinoin) causes remission of this leukemia by triggering the bodies' reorganization. As2O3 destroys the chimera, allowing new
SUMO-1 ubiquitinated PML to relocalize to nuclear bodies.[17] Retinoic acid induces a caspase-3 mediated degradation of the same chimera.[26]
In HHV,
ICP0 disrupts nuclear dots in the early stage of infection.[27]
References
^Weber SC (June 2017). "Sequence-encoded material properties dictate the structure and function of nuclear bodies". Current Opinion in Cell Biology. 46: 62–71.
doi:
10.1016/j.ceb.2017.03.003.
PMID28343140.
^Zimber A, Nguyen QD, Gespach C (October 2004). "Nuclear bodies and compartments: functional roles and cellular signalling in health and disease". Cellular Signalling. 16 (10): 1085–104.
doi:
10.1016/j.cellsig.2004.03.020.
PMID15240004.
^
abSternsdorf T, Grötzinger T, Jensen K, Will H (December 1997). "Nuclear dots: actors on many stages". Immunobiology. 198 (1–3): 307–31.
doi:
10.1016/s0171-2985(97)80051-4.
PMID9442402.
^Pawlotsky JM, Andre C, Metreau JM, Beaugrand M, Zafrani ES, Dhumeaux D (July 1992). "Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis". Hepatology. 16 (1): 127–31.
doi:
10.1002/hep.1840160121.
PMID1319948.
S2CID22729443.
^
abChaly N, Setterfield G, Kaplan JG, Brown DL (1983). "Nuclear bodies in mouse splenic lymphocytes: II - Cytochemistry and autoradiography during stimulation by concanavalin A". Biology of the Cell. 49 (1): 35–43.
doi:
10.1111/j.1768-322x.1984.tb00220.x.
PMID6199062.
S2CID43084163.
^Zuber M, Heyden TS, Lajous-Petter AM (1995). "A human autoantibody recognizing nuclear matrix-associated nuclear protein localized in dot structures". Biology of the Cell. 85 (1): 77–86.
doi:
10.1111/j.1768-322X.1995.tb00944.x.
PMID8882521.
^Maul GG, Yu E, Ishov AM, Epstein AL (December 1995). "Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress". Journal of Cellular Biochemistry. 59 (4): 498–513.
doi:
10.1002/jcb.240590410.
PMID8749719.
S2CID22209911.