Identification of sites on chromosomal protein HMG‐I phosphorylated by casein kinase II

Palvimo, Jorma J.; Linnala-Kankkunen, Annikka

doi:10.1016/0014-5793(89)81796-x

Cited by 54 publications

(60 citation statements)

References 25 publications

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“…1A). This phosphorylation reflects a constitutive modification found in native forms of these proteins (53)(54)(55). The free and DNA-bound proteins were digested with hydroxyl radicals, and the digestion products were separated by electrophoresis.…”

Section: High Mobility Group Proteins Hmgi Hmgy Hmgi-c and Chmgi Imentioning

confidence: 90%

“…Phosphorylation Affects Contacts of HMGY with DNA-Previous studies have shown that mammalian and insect HMGI/Y proteins are in vivo phosphorylated at several positions by CK2 (53)(54)(55) and Cdc2 kinase (56 -58). In some reports, a general phosphorylation-dependent attenuation of binding affinity of the proteins has been demonstrated (56 -60); however, the mechanism of these changes was not studied.…”

Section: Fig 5 Ethylation (A) and Methylation (B) Interference Analmentioning

confidence: 99%

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Distinct Organization of DNA Complexes of Various HMGI/Y Family Proteins and Their Modulation upon Mitotic Phosphorylation

Piekiełko¹,

Drung²,

Rogalla³

et al. 2001

Journal of Biological Chemistry

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High mobility group (HMG) proteins HMGI, HMGY, HMGI-C, and Chironomus HMGI are DNA-binding proteins thought to modulate the assembly and the function of transcriptional complexes. Each of these proteins contains three DNA-binding domains (DBD), properties of which appear to be regulated by phosphorylation. High levels of these proteins are characteristic for rapidly dividing cells in embryonic tissues and tumors. On the basis of their occurrence, specific functions for each of these proteins have been postulated. In this study we demonstrate differences in the nature of contacts of these proteins with promoter region of the interferon-␤ gene. We show that HMGI and HMGY interact with this DNA via three DBDs, whereas HMGI-C and Chironomus HMGI bind to this DNA using only two domains. Phos- Despite continuously increasing interest in the function(s) of this group of proteins, the nature of the interaction of these proteins with DNA is still not sufficiently understood. The proteins of the HMGI/Y family are 10 -11 kDa in size, are highly charged, are rich both in acidic and basic residues, are proline-rich, and contain only few residues with bulky hydrophobic side chains. This unusual amino acid composition inhibits folding of the polypeptide backbone of these proteins into any defined secondary structure. Common for HMGI/Y proteins is the presence of three putative DNA-binding domains (DBD), so called . NMR analysis of a complex of a peptide derived from HMGI(Y) bound to a short DNA fragment revealed that the centrally located RGR residues are essentially for binding and responsible for contacts of the protein with the bases and phosphate-sugar backbone (27). Alternative approaches, which used deletion and point-mutated proteins, revealed that two or three DBDs of the protein bind to DNA in a cooperative way (28 -30). Application of the protein-footprinting method for mapping of protein regions interacting with DNA (31) allowed more detailed characterization of the binding of HMGI(Y) proteins to DNA (32). A combination of this method

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Section: High Mobility Group Proteins Hmgi Hmgy Hmgi-c and Chmgi Imentioning

confidence: 90%

Section: Fig 5 Ethylation (A) and Methylation (B) Interference Analmentioning

confidence: 99%

Distinct Organization of DNA Complexes of Various HMGI/Y Family Proteins and Their Modulation upon Mitotic Phosphorylation

Piekiełko¹,

Drung²,

Rogalla³

et al. 2001

Journal of Biological Chemistry

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“…For HMGA1, it has been suggested that removal of the acidic tail has important implications for regulatory control of its binding affinity to DNA (32). This carboxyl-terminal acidic motif contains a consensus recognition sequence for casein kinase II, which phosphorylates HMGA1 in vitro and in vivo (41). Upon casein kinase II -dependent phosphorylation of HMGA1 in vivo, its affinity for DNA decreases (42).…”

Section: Discussionmentioning

confidence: 99%

Transactivation Functions of the Tumor-Specific HMGA2/LPP Fusion Protein Are Augmented by Wild-Type HMGA2

Crombez

Vanoirbeek

Ven

et al. 2005

Molecular Cancer Research

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The gene encoding the architectural transcription factor HMGA2 is frequently rearranged in several benign tumors of mesenchymal origin. The lipoma preferred partner (LPP) gene is the most frequent translocation partner of HMGA2 in a subgroup of lipomas, which are benign tumors of adipose tissue. In these lipomas, HMGA2/LPP fusion transcripts are expressed, which encode for the three AT-hooks of HMGA2 followed by the two most carboxyl-terminal LIM domains (protein-protein interaction domains) of LPP. Identical fusion transcripts are also expressed in other benign mesenchymal tumors. Previous studies revealed that the LIM domains of LPP have transcriptional activation capacity in GAL4-based luciferase reporter assays. Here, we show that the HMGA2/LPP fusion protein retains the transactivation functions of the LPP LIM domains and thus functions as transcription factor. The HMGA2/LPP fusion protein activates transcription from the well-characterized PRDII element, which is a part of the IFN-B B enhancer and which is known to bind to HMGA2. We also show that HMGA2/LPP activates transcription from the BAT-1 element of the rhodopsin promoter, a HMGA1-binding element. HMGA1 is a closely related family member of HMGA2. Finally, in a number of lipomas, HMGA2/LPP and HMGA2 are coexpressed, and HMGA2 augments the transactivation functions of HMGA2/LPP. These results support the concept that the transactivation functions of the novel HMGA2/LPP transcription factor contribute to lipomagenesis.

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“…They are phosphorylated by protein kinase CK2 (18,19) and, in a cell-cycle-and differentiation-dependent manner, by Cdc2 kinase (20 -22), mitogen-activated protein kinase, and protein kinase C (22). In vivo the entire population of the HMGI-C protein appears to be phosphorylated (23).…”

mentioning

confidence: 99%

Architecture of High Mobility Group Protein I-C·DNA Complex and Its Perturbation upon Phosphorylation by Cdc2 Kinase

Schwanbeck

Manfioletti

Wiśniewski

2000

Journal of Biological Chemistry

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The high mobility group I-C (HMGI-C) protein is an abundant component of rapidly proliferating undifferentiated cells. High level expression of this protein is characteristic for early embryonic tissue and diverse tumors. HMGI-C can function as an architectural factor enhancing the activity of transcription factor NF-B on the ␤-interferon promoter. The protein has three minor groove DNA-binding domains (AT-hooks). Here, we describe the complex of HMGI-C with a fragment of the ␤-interferon promoter. We show that the protein binds to NRDI and PRDII elements of the promoter with its first and second AT-hook, respectively. Phosphorylation by Cdc2 kinase leads to a partial derailing of the AThooks from the minor groove, affecting mainly the second binding domain. In contrast, binding to long AT stretches of DNA involves contacts with all three AThooks and is marginally sensitive to phosphorylation. Our data stress the importance of conformation of the DNA binding site and protein phosphorylation for its function.High mobility group proteins are abundant components of chromatin, which modulate DNA conformation and facilitate assembly of higher order structures (for a review, see Refs. 1 and 2). A subgroup of these proteins, the HMGI(Y) 1 family, comprises diverse proteins containing short DNA-binding domains (AT-hooks; Ref.3) and acidic C-terminal regions. They act as regulatory factors affecting indirectly the expression of genes (for a review see Ref. 4). High levels of the proteins were found in transcriptionally active chromatin (5) and in constitutive heterochromatin of metaphase chromosomes (6). In mammalian cells three proteins of this type were detected, the HMGI, HMGY, and HMGI-C (7, 8). They are abundantly expressed in embryonic, rapidly proliferating, and tumor cells. Rearrangements or impairing of the HMGI-C gene were found in a number of tumors of mesenchymal origin (9, 10) and lead to the pygmy phenotype (11), respectively. These observations emphasize involvement of this protein in cell growth and development.However, although different binding sites of HMGI(Y) proteins within gene enhancers and promoters have been described, the organization of this protein-DNA complex is poorly understood. The proteins have three putative AT-hooks that interact with the minor groove of DNA (12). Two of them are necessary for strong binding to DNA (13-15), and the involvement of particular AT-hooks depends on the DNA conformation (16). NMR studies of HMGI revealed that, in the protein-DNA complex, the central portion of the AT-hook, the tripeptide RGR, penetrates the minor groove of the AT-rich stretches, whereas residues on both sides of the peptide establish extensive contacts with the sugar-phosphate backbone (17). On the basis of the DNA-binding strength and extent of the contacts to the backbone, these DNA binding domains (DBD) were classified as type I DNA binding domains (I-DBD) and type II DBD with high and low binding affinity, respectively (17).The proteins of the HMGI(Y) family are phosphoproteins. They are ...

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Identification of sites on chromosomal protein HMG‐I phosphorylated by casein kinase II

Cited by 54 publications

References 25 publications

Distinct Organization of DNA Complexes of Various HMGI/Y Family Proteins and Their Modulation upon Mitotic Phosphorylation

Distinct Organization of DNA Complexes of Various HMGI/Y Family Proteins and Their Modulation upon Mitotic Phosphorylation

Transactivation Functions of the Tumor-Specific HMGA2/LPP Fusion Protein Are Augmented by Wild-Type HMGA2

Architecture of High Mobility Group Protein I-C·DNA Complex and Its Perturbation upon Phosphorylation by Cdc2 Kinase

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