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  There are four different types of splice variants in SP100 :  
 
  There are four different types of splice variants in SP100 :  
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* '''SP100A''', contains 480 amino acids - the most abundant form  
 
* '''SP100A''', contains 480 amino acids - the most abundant form  
 
* '''SP100-HMG''', the large variant, contain extra functional domains such as a SAND domain and a HMG box possesing a DNA-binding domain that can affect chromatin structure <ref> Zhong, S., Salomoni, P., & Pandolfi, P. (2000). The transcriptional role of PML and the nuclear body. Nature cell biology, 2(5), E85-E90.</ref>.
 
* '''SP100-HMG''', the large variant, contain extra functional domains such as a SAND domain and a HMG box possesing a DNA-binding domain that can affect chromatin structure <ref> Zhong, S., Salomoni, P., & Pandolfi, P. (2000). The transcriptional role of PML and the nuclear body. Nature cell biology, 2(5), E85-E90.</ref>.

Revision as of 04:50, 21 May 2009

Nuclear Body Protein SP100

SP100 protein was first identified as a nuclear autoimmune antigen in the patient suffering from autoimmune disease primary biliary cirrhosis. It is named after the weight and shape of 100-kDa Speckled protein. SP100 is part of the component in the nuclear body that may involve during the immune response by regulating the transcription process. Such work is done in conjunction with PML nuclear bodies whereby PML regulates the transcriptional activity and SP100 work to repress the action. [1]. Interferons (IFNs), a cytokine released during immune response can upregulate the transcription of SP100, especially during the cellular antigen response against virus. This transcription process also plays roles in autoimmunity and oncogenesis [2].

Structure

The SP100 and promyelocytic leukaemia proteins are often described as part of the components in subnuclear domain that makes nucelar dots (ND) or known as PML-SP100 nuclear bodies (NBs). The disruption of this ubiquitous structures can cause acute promyelocytic leukemia (APL) and it also invovles during DNA virus infection. SP100 protein and PML are covalently modified by the small ubiquitin-related protein SUMO-1. The modification requires nuclear localisation signal (NLS) and involves some lysine residue.


SP100 is also known to bind and interact with the members of heterochromatin protein 1 (HP1) families of non-histone chromosomal proteins. This protein present targets for the process of transcription, DNA replication and repair. Combined with one of its splice variants, HMG, SP100-HMG have the DNA-binding potential under a protein family of the high mobility group-1 (HMG-1). When all the three presents, SP100, HP1, and SP100-HMG, they can serve the function of transcriptional activity by attaching to the promotor. This type of SP100 were found to be concentrated within PML/SP100 nuclear bodies. [3].


As a protein family, Sp100 has subfamilies such as Sp110, Sp140/LYSp100 and the autoimmune regulator protein (AIRE) that share an amino-terminus HSR (homogeneously staining region) domain [4]. SP100 proteins also have different splice variant forms that contain distinct subnuclear localisation areas in PML-SP100 NB components [5]. These splice variants, are the one that could be modified covalently by SUMO-1 as well as conducting the activities at the chromatin level.


There are four different types of splice variants in SP100 : 
  • SP100A, contains 480 amino acids - the most abundant form
  • SP100-HMG, the large variant, contain extra functional domains such as a SAND domain and a HMG box possesing a DNA-binding domain that can affect chromatin structure [6].
  • SP100B
  • SP100C, a novel splice variant, that is homology to chromatin-associated factors. It contains distinct domain consisting of PHD finger-bromodomain motif.

The splice variants have differences between the domain compositions in carboxy termini yet all the four contain the same pattern in the amino-terminal domain. It has been speculated that this occurs so that they can carry on their functions separately, such as directing SP100 proteins at the NBs by N-terminal alone.

History

1984 Discovered as targets of autoantibodies in patients suffering from the autoimmune disease primary biliary cirrhosis.

1990 After the discovery, the protein was named SP100 (speckled protein of 100 kDa) after forming a 'speckle' shape in the nucleus by using sera from the patients.

1996 Identification of novel nuclear domain as a dot pattern.

1998 Novel protein motif, the HSR domain, was discovered , within this ND targeting/dimerisation domain.

2001 The fourth splice variant, SP100C was found from an isolated a partial cDNA of human liver.




Reference

HOMEWORK

Nucleus

Nucleus is one of the main components and only present in eukaryotic cell. It conducts DNA trascription to mRNA and mRNA need to be exported to cytoplasma to undergo translation to protein.

Nucleus has a double layer membranes that is connected to Endoplasmic Reticulum continuously. Cytoskeleton is also very crucial in order to hold the shape and structure of nucleus. The surface contains nuclear pores whereby passive transport of small ions and active transport of macromolecules can pass through.

Nuclear bodies contain specific compartments such as Cajal Bodies and PML bodies which fuctioning as modificator of small proteins and regulate the whole body's function respectively.


Mitochondria

What types of cellular processes require lots of energy from the mitochondria?

Complex animal cells need to retain energy from mitochondria through aerobic respiration. Mitochondria produce 15 times more ATP than anaerobic process which is required by the cells. The initial source is from glucose whereby it is processed and imported into mitochondria and undergo catabolism process such as Kerbs cycle, fatty acid oxidation, and amino acid oxidation.

Other examples are cell signalling, cell reproduction such as mitosis and meiosis.


Cell adhesion molecules (CAM)

Ng-CAM: Neuroglia Cell Adhesion Molecule

I-CAM: Intercellular Cellular Adhesion Molecule

L-CAM: Liver Cell Adhesion Molecule


Intermediate Filament

What is the name of the epidermal layer between the basal and granulosa layer and how does it relate to intermediate filaments?

Stratum spinosum is the


Confocal Microscopy

Two major types of Confocal microscope generate its signal are by:

  • Laser Systems for Confocal Microscopy

The source is from fluorophores whereby the biological molecules reach the excited state and emit ultraviolet or visible light photons and captures them to produce the image of specific structural components of the cells. The technique is advanced by the use of interference filters as well as Spectral Bleed-Through Artifacts (crossover or crosstalk) that is used for broad bandwidths and asymmetrical spectral profiles fluorophores. Laser Systems stimulates and amplifies the molecules with excess energy to emit light. It is the most common light source for scanning confocal fluorescence microscopy.

  • Non-Coherent (non-laser) Light Sources for Confocal Microscopy

This technique use traditional tungsten-halogen source and a short-arc lamp for fluorescence excitation.

  1. Zhong, S., Salomoni, P., & Pandolfi, P. (2000). The transcriptional role of PML and the nuclear body. Nature cell biology, 2(5), E85-E90.
  2. Seeler, J., Marchio, A., Losson, R., Desterro, J., Hay, R., Chambon, P., et al. (2001). Common properties of nuclear body protein SP100 and TIF1a chromatin factor: role of SUMO modification. Molecular and Cellular Biology, 21(10), 3314-3324.
  3. Zhong, S., Salomoni, P., & Pandolfi, P. (2000). The transcriptional role of PML and the nuclear body. Nature cell biology, 2(5), E85-E90.
  4. Möller, A., Sirma, H., Hofmann, T., Staege, H., Gresko, E., Lüdi, K., et al. (2003). Sp100 is important for the stimulatory effect of homeodomain-interacting protein kinase-2 on p53-dependent gene expression. Oncogene, 22(54), 8731-8737.
  5. Seeler, J., Marchio, A., Losson, R., Desterro, J., Hay, R., Chambon, P., et al. (2001). Common properties of nuclear body protein SP100 and TIF1a chromatin factor: role of SUMO modification. Molecular and Cellular Biology, 21(10), 3314-3324.
  6. Zhong, S., Salomoni, P., & Pandolfi, P. (2000). The transcriptional role of PML and the nuclear body. Nature cell biology, 2(5), E85-E90.