scholarly journals The family feud: turning off Sp1 by Sp1-like KLF proteins

2005 ◽  
Vol 392 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Gwen Lomberk ◽  
Raul Urrutia

Sp1 is one of the best characterized transcriptional activators. The biological importance of Sp1 is underscored by the fact that several hundreds of genes are thought to be regulated by this protein. However, during the last 5 years, a more extended family of Sp1-like transcription factors has been identified and characterized by the presence of a conserved DNA-binding domain comprising three Krüppel-like zinc fingers. Each distinct family member differs in its ability to regulate transcription, and, as a consequence, to influence cellular processes. Specific activation and repression domains located within the N-terminal regions of these proteins are responsible for these differences by facilitating interactions with various co-activators and co-repressors. The present review primarily focuses on discussing the structural, biochemical and biological functions of the repressor members of this family of transcription factors. The existence of these transcriptional repressors provides a tightly regulated mechanism for silencing a large number of genes that are already known to be activated by Sp1.

1993 ◽  
Vol 90 (23) ◽  
pp. 11361-11365 ◽  
Author(s):  
J D Licht ◽  
M Ro ◽  
M A English ◽  
M Grossel ◽  
U Hansen

The Krüppel (Kr) protein, bound at kilobase distances from the start site of transcription, represses transcription by RNA polymerase II in mammalian cells. Repression is monotonically dependent on the dose of Kr protein and the presence of Kr binding site(s) on the DNA. These data suggest an inhibitory protein-protein interaction between the Kr protein and proximal transcription factors. Repression by Kr depends on the specific activator protein driving transcription. In particular, Kr protein selectively represses transcription mediated by the Sp1 glutamine-rich activation domain, tethered to the promoter by a GAL4 DNA-binding domain, but does not repress transcription stimulated by the acidic GAL4 activator. We believe this represents repression by a quenching interaction between DNA-bound Kr protein and the activation region of Sp1, rather than competition between Sp1 and Kr for a limiting transcriptional component. Selective, context-related repression affords an added layer of combinatorial control of gene expression by sequence-specific transcription factors.


2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Shagufta H. Khan ◽  
Raj Kumar

A number of proteins with intrinsically disordered (ID) regions/domains are reported to be found disproportionately higher in transcription factors. Available evidences suggest that presence of ID region/domain within a transcription factor plays an important role in its biological functions. These ID sequences provide large flexible surfaces that can allow them to make more efficient physical and functional interactions with their target partners. Since transcription factors regulate expression of target genes by interacting with specific coregulatory proteins, these ID regions/domains can be used as a platform for such large macromolecular interactions, and may represent a mechanism for regulation of cellular processes. The precise structural basis for the function of these ID regions/domains of the transcription factors remains to be determined. In the recent years there has been growing evidence suggesting that an induced fit-like process leads to imposition of folded functional structure in these ID domains on which large multiprotein complexes are built. These multiprotein complexes may eventually dictate the final outcome of the gene regulation by the transcription factors.


2020 ◽  
Author(s):  
David Blom-Dahl ◽  
Sergio Córdoba ◽  
Hugo Gabilondo ◽  
Pablo Carr-Baena ◽  
Fernando J. Díaz-Benjumea ◽  
...  

AbstractThe Sp family of transcription factors plays important functions during development and disease. An evolutionary conserved role for some Sp family members is the control of limb development. The family is characterized by the presence of three C2H2-type zinc fingers and an adjacent 10 aa region with an unknown function called the Buttonhead (BTD) box. The presence of this BTD-box in all Sp family members identified from arthropods to vertebrates, suggests that it plays an important role during development. However, despite its conservation, the in vivo function of the BTD-box has never been studied. In this work, we have generated specific BTD-box deletion alleles for the Drosophila Sp family members Sp1 and buttonhead (btd) using gene editing tools and analyzed its role during development. Unexpectedly, btd and Sp1 mutant alleles that lack the BTD-box are viable and have almost normal appendages. However, in a sensitized background the requirement of this domain to fully regulate some of Sp1 and Btd target genes is revealed. Furthermore, we have also identified a novel Sp1 role promoting leg vs antenna identity through the repression of spineless (ss) expression in the leg, a function that also depends on the Sp1 BTD-box.


Development ◽  
2001 ◽  
Vol 128 (19) ◽  
pp. 3749-3758 ◽  
Author(s):  
Frank L. Conlon ◽  
Lynne Fairclough ◽  
Brenda M. J. Price ◽  
Elena S. Casey ◽  
J. C. Smith

Members of the T box family of transcription factors play important roles in early development. Different members of the family exert different effects and here we show that much of the specificity of the Xenopus T box proteins Xbra, VegT and Eomesodermin resides in the DNA-binding domain, or T box. Binding site selection experiments show that the three proteins bind the same core sequence, but they select paired sites that differ in their orientation and spacing. Lysine 149 of Xbra is conserved in all Brachyury homologues, while the corresponding amino acid in VegT and Eomesodermin is asparagine. Mutation of this amino acid to lysine changes the inductive abilities of VegT and Eomesodermin to resemble that of Xbra.


2013 ◽  
Vol 35 (10) ◽  
pp. 1179-1188 ◽  
Author(s):  
Hong WANG ◽  
Gang-Bo LI ◽  
Da-Yong ZHANG ◽  
Jing LIN ◽  
Bao-Long SHENG ◽  
...  

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 741-741
Author(s):  
David Lombard

Abstract Sirtuins are NAD+-dependent deacylases that regulate diverse cellular processes such as metabolic homeostasis and genomic integrity. Mammals possess seven sirtuin family members, SIRT1-SIRT7, that display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions. Three sirtuins, SIRT3, SIRT4, and SIRT5, are primarily located in the mitochondrial matrix. SIRT5 is a very inefficient deacetylase, instead removing negatively charged post-translational modifications (succinyl, glutaryl, and malonyl groups) from lysines of its target proteins, in mitochondria and throughout the cell. SIRT5 plays only modest known roles in normal physiology, with its major functions occurring in the heart under stress conditions. In contrast, in specific cancer types, including melanoma, we have identified a major pro-survival role for SIRT5. We have traced this function of SIRT5 to novel roles for this protein in regulating chromatin biology. New insights into mechanisms of SIRT5 action in cancer, and in normal myocardium, will be discussed.


2021 ◽  
Vol 713 ◽  
pp. 109060
Author(s):  
Neetu Neetu ◽  
Madhusudhanarao Katiki ◽  
Jai Krishna Mahto ◽  
Monica Sharma ◽  
Anoop Narayanan ◽  
...  

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maria Rita Blanco ◽  
Mariela N. Golik

PurposeThe career is a space where family and work lives amalgamate. The role of work for the individual, and the meaning of work within the culture, will determine the relevance of family. This study investigates CEOs' perception about conjugal family influence on career decisions, and it examines family factors.Design/methodology/approachThrough a qualitative study, 22 Latin American CEOs who work for multinational firms were interviewed in a semi-structured way.FindingsNot all career decisions were influenced by conjugal family. CEOs varied in the extent to which they considered their families when reflecting on their career decisions. Expatriation, joining or quitting an organization and change of area of work were found as those decisions perceived to be influenced by conjugal family. Family support, family structure and family demands and responsibilities were identified as the family factors involved. In spite of the role salience, family factors influenced some of CEOs' career decisions, in part, due to the cultural characteristics of the Latin American environment. The instrumental support of the extended family, as part of collectivist societies, was also evidenced.Practical implicationsA better understanding of the family influenced decisions and family factors involved may enhance individual career decision-making as well as organizational career management processes and public initiatives.Originality/valueThis study contributes to family and career literature, being the first one to explore the conjugal family influence upon CEOs' career decisions.


2009 ◽  
Vol 90 (2) ◽  
pp. 227-230 ◽  
Author(s):  
Joan Beder

When an individual dies, the role of the family member(s) is clearly prescribed by society: support, presence, caring, and remembrance. Traditionally, the definition of “family” has broadened to create the “extended family” or “expanded family” with members defined by deep bonds, relationships, and friendships. Currently, close friends who become the extended/expanded family, can be as central as kin to family structure and stability. Therefore, when one member of an extended family dies, the death resonates throughout the entire system affecting not only the lives of the immediate family members, but also those in the expanded circle of family relationships. This article describes the relationships in one extended family and discusses the struggles and counseling interventions used when one member of an extended family suddenly dies.


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