DNA binding activities

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

NFAT was initially identified in activated T cells as a DNA binding activity required for IL-2 expression, a cytokine that plays a key role in T cell activation and survival. Subsequent studies revealed the involvement... 

Beside other functions in signal transduction, protein inhibitors of activated STAT suppress the DNA-binding activity of STAT proteins. 

The human HS cycle can be considered broadly as a period which leads to the dramatic shift in activities of the transcriptional and translational machinery followed by eventual recovery and resumption of original activities preceding stress. Figure 1 depicts many of the key events in the HS cycle for a typical human cell line such as cervical carcinoma-derived HeLa cells. Most cells respond in an identical fashion, but some cell types that have distinctive HS responses. These differences are manifested by shifts in the relative concentrations of accumulated HS proteins and possibly in the pattern of posttranslational modifications. In all cases, however, the cellular stress response is heralded by induction of a specific transcription factor whose DNA binding activity facilitates increased expression of one or more of the stress-inducible genes. 

HSFl phosphorylation must be sensitive to nonheat inducers of HSF-DNA binding activity because HSFl phosphorylation can be achieved at 37 °C by other inducers of the HS response. HSF 1 contains polypeptide sequences that could serve as substrates for well characterized protein kinases, but few of these are known to be heat inducible. One family of protein kinases, the S6 protein kinases, have already been shown to exhibit heat inducible activity however, their peak level of activity during HS occurs well after the maximal induction of HSF phosphorylation (Jurivich et al., 1991). Thus, other protein kinases are likely to be directly linked to the phosphorylation of HSF. Some of the putative protein phosphorylation sites on HSF include motifs for protein kinase C, casein kinase, and enterokinase. There are tyrosine sequences that match substrates for known tyrosine kinases, but whether these residues are accessible to phosphorylation is not established. 

Mosser, D.D., Duchaine, J., Massie, B. (1993). The DNA binding activity of the human heat shock transcription factor is regulated in vivo by hsp70. Mol. Cell. Biol. 13, 5427-5438. 

Sarge, K.D., Murphy, S.P., Morimoto, R.l. (1993). Activation of heat shock gene transcription by heat shock factor 1 involves oligomenzation, acquisition of DNA binding activity, and nuclear localization and can occur in the absence of stress. Mol. Cell. Biol. 13. 1392-1407. 

NF-xB, originally defined as the enhancer of kappa light-chain expression in B lymphocytes, is a hcterodimeric protein that can rapidly activate several genes associated with the inflammatory process (reviewed by Schreck et al., 1992). The DNA binding, nuclear form, of NF-xB is a heterodimer composed of one Rel-A (65 kD) and one p50 (50 kD) subunit. However, both subunits can form homodimers that also have DNA-binding activity. The inactive form of NF-xB in non-stimulated cells is localized to the cytoplasm of resting cells, and is bound to its inhibitor IxB. 

Palozza, P, S Serini, A Torsello et al. 2003. Beta-carotene regulates NF-kappa B DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. J Nutr 133 381-388. 

Recent studies have demonstrated that lithium (and to a lesser extent VPA) produces, at therapeutically relevant concentrations, complex alterations in basal and/or stimulated DNA-binding of 12-o-tetradecanoyl-phorbol 13-acetate (TPA) response element (TRE) to AP-1 transcription factors. These alterations are produced not only in human SH-SY5Y cells in vitro, but also in rodent brain following chronic, in vivo administration [5, 7, 15-21]. Corresponding to an increase in basal AP-1 DNA-binding activity, lithium and VPA have been shown to increase the expression of a luciferase reporter gene driven by an SV40 promoter that contains TREs in a time- and concentration-dependent fashion. Mutations in the TRE... 

Asghari V, Reiach JS, Young LT. Differential effects of mood stabilizers on Fos/ Jun proteins and AP-1 DNA binding activity in human neuroblastoma SH-SY-5Y cells. Mol Brain Res 1998 58 95-102. 

Uniap MT. Lithium attenuates nerve growth factor-induced activation of AP-1 DNA binding activity in PC12 cells. Neuropsychopharmacology 1997 17 12-17. 

Williams MB. Circadian variation in rat brain AP-1 DNA binding activity after cholinergic stimulation modulation by lithium. Psychopharmacology (Berlin), 1995 122 363-368. 

WILLIAMS, C.E., GROTEWOLD, E., Differences between plant and animal Myb domains are fundamental for DNA binding activity and chimeric Myb domains have novel DNA-binding specificities, J. Biol. Chem., 1997, 272, 563-571. 

Hu, Y., Jin, X., and Snow, E.T., Effect of arsenic on transcription factor AP-1 and Nfkap-paB DNA binding activity and related gene expression, Toxicol. Lett., 133, 33, 2002. 

Nucleolin together with HnRNP D has been shown to form the LRl transcription factor. LRl is a B cell-specific, sequence-specific DNA binding activity that regulates transcription in activated B cells (Hanakahi et at, 1997 Hanakahi and Maizels, 2000). DNA bending induced by nucleolin and hnRNP D might regulate the transcriptional activation by LRl (Hanakahi and Maizels, 2000). 

Raziuddin A, Court D, Sarkar FH, Liu YL, Kung H, Raziuddin R (1997) A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor tissues mediates NF-kappaB DNA binding activity. / Biol Chem 272(25) 15715-15720... 

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