Dataset Information

TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1.

ABSTRACT: Certain proteins can undergo polyglycylation and polyglutamylation. Polyglutamylases (glutamate ligases) have recently been identified in a family of tubulin tyrosine ligase-like (TTLL) proteins. However, no polyglycylase (glycine ligase) has yet been reported. Here we identify a polyglycylase in the TTLL proteins by using an anti-poly-glycine antibody. The antibody reacted with a cytoplasmic 60-kDa protein that accumulated in elongating spermatids. Using tandem mass spectrometry of trypsinized samples, immunoprecipitated by the antibody from the TTLL10-expressing cells, we identified the 60-kDa protein as nucleosome assembly protein 1 (NAP1). Recombinant TTLL10 incorporated glycine into recombinant NAP1 in vitro. Mutational analyses indicated that Glu residues at 359 and 360 in the C-terminal part of NAP1 are putative sites for the modification. Thus, TTLL10 is a polyglycylase for NAP1.

SUBMITTER: Ikegami K

PROVIDER: S-EPMC2408875 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1.

Ikegami Koji K Horigome Daisuke D Mukai Masahiro M Livnat Itamar I MacGregor Grant R GR Setou Mitsutoshi M

FEBS letters 20080310 7

Certain proteins can undergo polyglycylation and polyglutamylation. Polyglutamylases (glutamate ligases) have recently been identified in a family of tubulin tyrosine ligase-like (TTLL) proteins. However, no polyglycylase (glycine ligase) has yet been reported. Here we identify a polyglycylase in the TTLL proteins by using an anti-poly-glycine antibody. The antibody reacted with a cytoplasmic 60-kDa protein that accumulated in elongating spermatids. Using tandem mass spectrometry of trypsinized ...[more]

PMID: 18331838

Similar Datasets

Project description:Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV infection is the viral nonstructural protein NS5A, which, in addition to its role in replication and assembly, targets several pathways involved in the cellular response to viral infection. Several unbiased screens identified nucleosome assembly protein 1-like 1 (NAP1L1) as an interaction partner of HCV NS5A. Here we confirmed this interaction and mapped it to the C terminus of NS5A of both genotype 1 and 2. NS5A sequesters NAP1L1 in the cytoplasm, blocking its nuclear translocation. However, only NS5A from genotype 2 HCV, and not that from genotype 1, targets NAP1L1 for proteosome-mediated degradation. NAP1L1 is a nuclear chaperone involved in chromatin remodeling, and we demonstrated the NAP1L1-dependent regulation of specific pathways involved in cellular responses to viral infection and cell survival. Among those, we showed that lack of NAP1L1 leads to a decrease of RELA protein levels and a strong defect of IRF3 TBK1/IKK?-mediated phosphorylation, leading to inefficient RIG-I and Toll-like receptor 3 (TLR3) responses. Hence, HCV is able to modulate the host cell environment by targeting NAP1L1 through NS5A.IMPORTANCE Viruses have evolved to replicate and to overcome antiviral countermeasures of the infected cell. Hepatitis C virus is capable of establishing a lifelong chronic infection in the liver, which could develop into cirrhosis and cancer. Chronic viruses are particularly able to interfere with the cellular antiviral pathways by several different mechanisms. In this study, we identified a novel cellular target of the viral nonstructural protein NS5A and demonstrated its role in antiviral signaling. This factor, called nucleosome assembly protein 1-like 1 (NAP1L1), is a nuclear chaperone involved in the remodeling of chromatin during transcription. When it is depleted, specific signaling pathways leading to antiviral effectors are affected. Therefore, we provide evidence for both a novel strategy of virus evasion from cellular immunity and a novel role for a cellular protein, which has not been described to date.

Dataset Information

TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1.

Publications

TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets