Nuclear tumor suppressor

Nuclear tumor suppressors inhibit return to the cell cycle in fully differentiated cells. The genes that code for these proteins are referred to as anti-oncogenes due to this function. On the role of p53 and pRb, see p.394. 

Mutations affecting the Swi/Snf chromatin-remodeling complex, which participates in transcriptional control, are associated with a variety of tumors. In some cases, interaction of the Swi/Snf complex with a nuclear tumor-suppressor protein may have a repressing effect on gene expression. 

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

Park J, Wood M A, Cole MD (2002) BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation. Mol Cell Biol 22 1307-1316 Park JH, Roeder RG (2006) GAS41 Is Required for Repression of the p53 Tumor Suppressor Pathway... 

A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31. Oncogene,... 

Hochstrasser M (1998) There s the rub a novel ubiquitin-like modification linked to cell cycle regulation. Genes Dev 12 901-907 Hochstrasser M, Johnson PR, Arendt CS, Amerik AY, Swaminathan S, Swanson R, Li SJ, Laney J, P s Ryiaarsdam R, Now J, Connerly PL (1999) The Saccharomyces cerevisiae ubiquitin-proteasome system. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 354 1513-1522 Honda R, Tanaka, H Yasuda H (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420 25-27 Hood JK, Silver PA (1999) In or out Regulating nuclear transport. Curr Opin Ceil Biol 11 241-247... 

The histone deacetylases are found in large protein complexes, often together with repressive transcription factors. By this token, interactions of the repressive heterodi-meric transcription factor Mad-Max and a complex with the histone deacetylase HDAC I and the mSinSA protein have been demonstrated. A complex of HDAC I and the nuclear receptor-corepressor (see chapter 4) binds to unliganded nuclear receptors and is believed to exercise a repressive effect. A further example is the tumor suppressor protein pRb (see chapters 13,14), which can occur as a transcription repressor in the hypo-phosphorylated form and transcriptionally activating in the hyperphosphorylated form. The repressive form of the pRb protein recruits the histone deacetylase HDAC 1 to the DNA and thereby initiates an active repression of the gene (see 13.3.2). 

NF-icB, Nuclear factor-kappaB GFAP, glial fibrillary acidic protein /3-APP, /3-amyloid precursor protein TGF-/33, transforming growth factor-/33 Cdk4, cyclin-dependent kinase and p53, a tumor-suppressor gene. 

There are two basic mechanisms that describe how HDAC inhibitors may function in cancer therapy, by either inhibition of cell proliferation or induction of apoptosis (105). The inhibition of cell proliferation and differentiation occurs by supporting nuclear receptor response driving terminal cell differentiation, reversal of repression by fusion transcription factors or over-expressed repressors, induction of p21, G1 arrest, and cellular differentiation, reactivation of silenced tumor suppressor genes, and suppression... 

Persad S, Troussard AA, McPhee TR, Mulholland DJ, Dedhar S. Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation. J. Cell. Biol. 2001 153 1161-1174. Yang Y, Guo L, Blattner SM, Mundel P, Kretzler M, Wu C. Formation and phosphorylation of the PINCH-l-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podoc)4e adhesion, architecture, and survival. J. Am. Soc. Nephrol. 2005 16 1966-1976. 

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