Cloning of Novel Injury-regulated Genes

Munz, Barbara; Lochmüller, Hanns; Werner, Sabine

doi:10.1074/jbc.274.19.13305

Cited by 28 publications

(10 citation statements)

References 18 publications

(24 reference statements)

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“…Yotov and St-Arnaud have also published that ␣NAC binds to a highly redundant consensus DNA sequence and thereby is implicated in transcription activation (25). Consistent with this idea, it has been reported that a tissue-specific isoform of ␣NAC (skNAC) is up-regulated in differentiating myoblasts and osteoblasts and in cells involved in wound healing (24,25,39,40). Note, however, that all biochemical activities reported up to now have been for ␣NAC and not skNAC.…”

Section: Discussionmentioning

confidence: 53%

The α and β Subunit of the Nascent Polypeptide-associated Complex Have Distinct Functions

Beatrix

Sakai

Wiedmann

2000

Journal of Biological Chemistry

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Nascent polypeptide-associated complex (NAC) is probably the first cytosolic protein to contact nascent polypeptide chains emerging from ribosomes. In this way NAC prevents inappropriate interactions with other factors. Eventually other factors involved in targeting and folding, like the Signal Recognition Particle or cytosolic chaperones, must gain access to the nascent chain. All NAC preparations to date consist of two copurifying polypeptides. Here we rigorously show that these two polypeptides, termed ␣-and ␤NAC, form a very stable complex in vivo and in vitro and that a functional complex can be reconstituted from the individual subunits. A dissection of the contributions of the individual subunits to NACs function revealed that both subunits are in direct contact with nascent polypeptide chains on the ribosome and that both contribute to the prevention of inappropriate interactions. However, ␤NAC alone directly binds to the ribosome and is sufficient to prevent ribosome binding to the endoplasmic reticulum membrane. Nascent polypeptide-associated complex (NAC) 1 is a very abundant cytosolic protein, which is involved in cotranslational targeting of polypeptides to the endoplasmic reticulum (ER) membrane. The intracellular NAC concentration varies only slightly in different tissues, ranging from 3 to 10 M (1). NAC is highly conserved among eukaryotes, but up to now no functional prokaryotic homolog has been described. The importance of NACs in vivo function is emphasized by early embryonically lethal phenotypes of NAC mutants in mice and fruit flies (2, 3). Recently it was also shown that yeast NAC, although not essential for growth (4), is involved in the import of proteins into mitochondria (5, 6).NAC was originally identified as a ribosome-associated protein when we set out to probe the molecular environment of growing polypeptides on the ribosome using a photo-cross-linking approach (7). With this technique we were able to show that NAC can interact with regions of nascent chains as close as 17 amino acids to the peptidyl transferase center. Additionally, it was shown by protease protection that NAC functions as a dissociable wall of a ribosomal tunnel through which the growing polypeptide emerges (8). Cycles of binding and releasing NAC expose the polypeptide to the cytosol in "quantal units" rather than amino acid by amino acid. We have proposed that exposing the polypeptide chain in functional units contributes to fidelity in cotranslational processes such as targeting and folding (9). Depleting NAC from translating ribosomes led to at least two inappropriate interactions. First, the signal recognition particle (SRP), which interacts with signal peptides of nascent chains on ribosomes during targeting to the ER membrane, could be cross-linked to nascent chains lacking signal peptides (7). Second, in the absence of NAC ribosomes translating non-secretory polypeptides inappropriately interacted with translocation sites on ER membranes and the signal-less chains were even translocated, although with l...

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Section: Discussionmentioning

confidence: 53%

The α and β Subunit of the Nascent Polypeptide-associated Complex Have Distinct Functions

Beatrix

Sakai

Wiedmann

2000

Journal of Biological Chemistry

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“…In addition to HSP90, SmyD1 may interact with other proteins to regulate gene expression and muscle cell differentiation. SmyD1 interacts with skNAC, a heart and muscle-specific transcription factor involved in muscle regeneration (51)(52)(53). Moreover, SmyD1 represses gene transcription in an HDAC-dependent manner (22).…”

Section: Smyd1a and Smyd1bmentioning

confidence: 99%

SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos

Tan

Rotllant²,

Li³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

203

289

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Histone modification has emerged as a fundamental mechanism for control of gene expression and cell differentiation. Recent studies suggest that SmyD1, a novo SET domain-containing protein, may play a critical role in cardiac muscle differentiation. However, its role in skeletal muscle development and its mechanism of actions remains elusive. Here we report that SmyD1a and SmyD1b, generated by alternative splicing of SmyD1 gene, are histone methyltransferases that play a key role in skeletal and cardiac muscle contraction. SmyD1a and SmyD1b are specifically expressed in skeletal and cardiac muscles of zebrafish embryos. Knockdown of SmyD1a and SmyD1b expression by morpholino antisense oligos resulted in malfunction of skeletal and cardiac muscles. The SmyD1 morphant embryos (embryos injected with morpholino oligos) could not swim and had no heartbeat. Myofibril organization in the morphant embryos was severely disrupted. The affected myofibers appeared as immature fibers with centrally located nuclei. Together, these data indicate that SmyD1a and SmyD1b are histone methyltransferases and play a critical role in myofibril organization during myofiber maturation.

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“…Further studies suggested that skNAC functions as a transcriptional coactivator (18). skNAC has been implicated in controlling myogenic differentiation, and skNAC transcripts are expressed at high levels only in skeletal and cardiac muscle (18,19). skNAC mRNA is also induced in myoblasts of the panniculus carnosus within 12 h following skin injury, a finding that may reflect an early role for skNAC in muscle repair (19).…”

mentioning

confidence: 96%

“…m-Bop and skNAC Are Induced and Colocalize during Skeletal Myogenesis-Previous studies have shown that skNAC transcripts are induced early during skeletal myogenesis (18,19). Having obtained evidence for interaction of m-Bop isoforms and skNAC, we examined the kinetics of expression and localization of m-Bop and skNAC in differentiating C2C12 myoblasts.…”

Section: M-bop and Sknac Interact In The Yeastmentioning

confidence: 99%

“…skNAC has been implicated in controlling myogenic differentiation, and skNAC transcripts are expressed at high levels only in skeletal and cardiac muscle (18,19). skNAC mRNA is also induced in myoblasts of the panniculus carnosus within 12 h following skin injury, a finding that may reflect an early role for skNAC in muscle repair (19). We report here that m-Bop and skNAC interact in vitro and in vivo and display similar kinetics of expression during skeletal myogenesis in culture, suggesting an associated role for m-Bop and skNAC in striated muscle myogenesis.…”

mentioning

confidence: 99%

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m-Bop, a Repressor Protein Essential for Cardiogenesis, Interacts with skNAC, a Heart- and Muscle-specific Transcription Factor

Sims

Weihe

Zhu

et al. 2002

Journal of Biological Chemistry

121

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The m-Bop protein encoded by the mouse Bop gene is strongly expressed in heart and skeletal muscle, and recent studies with Bop knockout mice have demonstrated that m-Bop is essential for cardiogenesis in vivo and can act as a HDAC-dependent repressor in vitro. In the present studies, m-Bop was observed to interact with skNAC, a reported transcriptional activator specific to heart and skeletal muscle. The amino-terminal S region of the split S-ET domain of m-Bop as well as the MYND domain were required for interaction with skNAC in both the two-hybrid system and in coimmunoprecipitation experiments from cultured mammalian cells. As shown previously for interaction of the MYND domain-containing transcriptional corepressor, BS69, with several viral and cellular oncoproteins, a PXLXP motif in skNAC was required for interaction with mBop. Similar kinetics of induction and localization of m-Bop and skNAC during the induction of myogenesis in cultured C2C12 cells suggests a possible associated role for these proteins during this process.The control of skeletal and cardiac maturation is ordered in a complex cascade of transcriptional activation and repression. The MyoD and MEF2 families of transcription factors dictate important developmental events that result in the formation of mature skeletal muscle. The MyoD family is comprised of the basic helix-loop-helix proteins MyoD, Myf5, MRF4, and myogenin. These myogenic regulators form heterodimers with the ubiquitous basic helix-loop-helix E proteins that subsequently activate key elements needed for the myogenic program (1). The MEF2 family is defined by the MADS domain and consists of MEF2A, MEF2B, MEF2C, and MEF2D. Members of the MEF2 family are expressed in tissues besides skeletal muscle including cardiac tissue, neurons, and T cells (2). Together, the MyoD and MEF2 families cooperate directly and indirectly to transduce the requisite signals for proper skeletal muscle formation.The discovery of chamber-specific transcription factors, such as the Hand1 and Hand2 proteins, has revealed the complex nature of cardiac transcriptional regulation (3). The list of genes that correspond to specific cardiac defects continues to grow, whereas the molecular nature of these defects remains largely elusive (4). To further understand the molecular underpinnings of cardiac development, it is critical to identify the relationships of transcriptional regulators shown to be important in cardiac morphogenesis.The Bop gene encodes distinct proteins expressed in skeletal and cardiac muscle, as well as in cytotoxic T lymphocytes. The Bop proteins found in skeletal muscle (m-Bop) and cytotoxic T lymphocytes (t-Bop) are identical over 90% of their primary amino acid sequence, differing only at their extreme amino terminus (5). Bop contains the evolutionarily conserved MYND and SET domains found in transcriptional regulators linked to development, chromatin stability, and cancer. The MYND domains in the transcriptional regulators ETO (MTG8) and BS69 function as protein-protein interaction d...

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Cloning of Novel Injury-regulated Genes

Cited by 28 publications

References 18 publications

The α and β Subunit of the Nascent Polypeptide-associated Complex Have Distinct Functions

The α and β Subunit of the Nascent Polypeptide-associated Complex Have Distinct Functions

SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos

m-Bop, a Repressor Protein Essential for Cardiogenesis, Interacts with skNAC, a Heart- and Muscle-specific Transcription Factor

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