LaiChu Wu - Academia.edu (original) (raw)

Papers by LaiChu Wu

Research paper thumbnail of The κB transcriptional enhancer motif and signal sequences of V(D)J recombination are targets for the zinc finger protein HIVEP3/KRC: a site selection amplification binding study

BMC Immunology, 2002

BACKGROUND: The ZAS family is composed of proteins that regulate transcription via specific gene ... more BACKGROUND: The ZAS family is composed of proteins that regulate transcription via specific gene regulatory elements. The amino-DNA binding domain (ZAS-N) and the carboxyl-DNA binding domain (ZAS-C) of a representative family member, named κB DNA binding and recognition component (KRC), were expressed as fusion proteins and their target DNA sequences were elucidated by site selection amplification binding assays, followed by

Research paper thumbnail of Molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V (D) J recombination

The somatic V(D)J recombination for the assembly of the Ig and TCR genes is mediated by the recom... more The somatic V(D)J recombination for the assembly of the Ig and TCR genes is mediated by the recombination signal sequences (Rss) and the V(D)J recombinase. A cDNA clone was isolated from a Xgtl 1 expression library made from mouse thymocyte poly(A)+ RNA, using the Rss as a ligand. The deduced amino acid sequence of the putative protein, designated Recognition component (Rc), reveals a pair of Cys2-His2 zinc fingers followed by a Gluand Asp-rich acidic domain. In addition, there are five copies of the Ser/Thr-Pro-X-Arg/Lys sequence, which are putative DNA binding units. The zinc finger-acidic domain structures present in Rc are also found in several enhancer binding proteins, such as those for the xB motif of the Ig x light chain enhancer or related sequences. Bacterial fusion proteins for Rc bind preferentially to the Rss heptamer and to the xB motif. The dual affinities of Rc for the Rss heptamer and the xB motif suggest a possible link between Ig transcription and somatic recombination. The formation of multiple 'gel-shifted' DNAprotein complexes for Rc and its DNA ligand suggests that these complexes tend to multimerize.

Research paper thumbnail of Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC

Genes, …, 2002

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B ... more The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2-deficient blastocyst complementation animal model. KRC-deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2 Ϫ/Ϫ blastocysts to generate KRC Ϫ/Ϫ ;RAG2 Ϫ/Ϫ chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4 ϩ CD8 ϩ thymocytes in the chimeras, suggesting that KRC may be involved in T-lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC Ϫ/Ϫ embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC-deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor-suppresser gene.

Research paper thumbnail of Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC

Genes, …, 2002

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B ... more The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2-deficient blastocyst complementation animal model. KRC-deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2 Ϫ/Ϫ blastocysts to generate KRC Ϫ/Ϫ ;RAG2 Ϫ/Ϫ chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4 ϩ CD8 ϩ thymocytes in the chimeras, suggesting that KRC may be involved in T-lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC Ϫ/Ϫ embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC-deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor-suppresser gene.

Research paper thumbnail of The κB transcriptional enhancer motif and signal sequences of V(D)J recombination are targets for the zinc finger protein HIVEP3/KRC: a site selection amplification binding study

BMC Immunology, 2002

BACKGROUND: The ZAS family is composed of proteins that regulate transcription via specific gene ... more BACKGROUND: The ZAS family is composed of proteins that regulate transcription via specific gene regulatory elements. The amino-DNA binding domain (ZAS-N) and the carboxyl-DNA binding domain (ZAS-C) of a representative family member, named κB DNA binding and recognition component (KRC), were expressed as fusion proteins and their target DNA sequences were elucidated by site selection amplification binding assays, followed by

Research paper thumbnail of Molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V (D) J recombination

The somatic V(D)J recombination for the assembly of the Ig and TCR genes is mediated by the recom... more The somatic V(D)J recombination for the assembly of the Ig and TCR genes is mediated by the recombination signal sequences (Rss) and the V(D)J recombinase. A cDNA clone was isolated from a Xgtl 1 expression library made from mouse thymocyte poly(A)+ RNA, using the Rss as a ligand. The deduced amino acid sequence of the putative protein, designated Recognition component (Rc), reveals a pair of Cys2-His2 zinc fingers followed by a Gluand Asp-rich acidic domain. In addition, there are five copies of the Ser/Thr-Pro-X-Arg/Lys sequence, which are putative DNA binding units. The zinc finger-acidic domain structures present in Rc are also found in several enhancer binding proteins, such as those for the xB motif of the Ig x light chain enhancer or related sequences. Bacterial fusion proteins for Rc bind preferentially to the Rss heptamer and to the xB motif. The dual affinities of Rc for the Rss heptamer and the xB motif suggest a possible link between Ig transcription and somatic recombination. The formation of multiple 'gel-shifted' DNAprotein complexes for Rc and its DNA ligand suggests that these complexes tend to multimerize.

Research paper thumbnail of Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC

Genes, …, 2002

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B ... more The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2-deficient blastocyst complementation animal model. KRC-deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2 Ϫ/Ϫ blastocysts to generate KRC Ϫ/Ϫ ;RAG2 Ϫ/Ϫ chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4 ϩ CD8 ϩ thymocytes in the chimeras, suggesting that KRC may be involved in T-lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC Ϫ/Ϫ embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC-deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor-suppresser gene.

Research paper thumbnail of Developmental anomalies and neoplasia in animals and cells deficient in the large zinc finger protein KRC

Genes, …, 2002

The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B ... more The large zinc finger protein KRC binds to the signal sequences of V(D)J recombination and the B motif. Disruption of KRC expression in cell lines resulted in increased cell proliferation, anchorage independence of growth, and uncoupling of nuclear division and cell division. In this report, the function of KRC was studied in a RAG2-deficient blastocyst complementation animal model. KRC-deficient embryonic stem cells were generated by homologous recombination and were introduced into RAG2 Ϫ/Ϫ blastocysts to generate KRC Ϫ/Ϫ ;RAG2 Ϫ/Ϫ chimeric mice. The lymphoid compartments of chimeras examined at 5 weeks of age were developed, suggesting that KRC is not essential for V(D)J recombination development. However, by 6 months of age, there was a marked deficit in CD4 ϩ CD8 ϩ thymocytes in the chimeras, suggesting that KRC may be involved in T-lymphocyte survival. Additionally, one chimera developed anomalies, including postaxial polydactyly, hydronephrosis, and an extragonadal malignant teratoma. DNA analysis showed that the teratoma was derived from KRC Ϫ/Ϫ embryonic stem cells. The teratoma had compound tissue organization and was infiltrated with B lymphocytes. Subsequently, several immortalized KRC-deficient cell lines were established from the teratoma. In this study, growth anomalies and neoplasia were observed in animals and cells deficient in KRC, and other studies have shown allelic loss occurring at the chromosomal region of the human KRC counterpart in various tumors. We propose that KRC may be a previously unidentified tumor-suppresser gene.