A cluster of hematopoietic serine protease genes is found on the same chromosomal band as the human alpha/delta T-cell receptor locus.

Hanson, Robin; Hohn, Patricia A.; Popescu, Nicholas C.; Ley, Timothy J.

doi:10.1073/pnas.87.3.960

Cited by 56 publications

(19 citation statements)

References 37 publications

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“…These sequences map within a locus (14q11.2 for human and 14C1 for mouse) that harbors a number of genes playing essential cellular functions (apoptosis, chromosome ends maintenance, immune system): the neural retina leucine zipper (NRL) gene (25,26), the adenylate cyclase-4 (ADCY4) gene (27), the CCAAT/enhancer-binding protein (C/EBP), epsilon gene (28), the granzyme B and H genes (29,30), the T-cell antigen receptor, ␣ polypeptide (TCRA) (31)(32)(33) and ⌬ polypeptide genes (TCRD) (34), the telomeraseassociated protein-1 (TEP1) gene (35), BCL2-like 2 (BCL2L2) (36), and the APEX nuclease (multi-functional DNA repair enzyme) gene (37). A number of chromosomal abnormalities within this portion of chromosome 14, mainly translocations, have been found in a variety of human germ cell tumors, adenocarcinoma, leukemia, and lymphoma.…”

Section: Discussionmentioning

confidence: 99%

A Bidirectional Promoter Connects the Poly(ADP-ribose) Polymerase 2 (PARP-2) Gene to the Gene for RNase P RNA

Amé

Schreiber

Fraulob

et al. 2001

Journal of Biological Chemistry

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Poly(ADP-ribose) polymerase 2 (PARP-2) is a DNA damage-dependent enzyme that belongs to a growing family of enzymes seemingly involved in genome protection. To gain insight into the physiological role of PARP-2 and to investigate mechanisms of PARP-2 gene regulation, we cloned and characterized the murine PARP-2 gene. The PARP-2 gene consists of 16 exons and 15 introns spanning about 13 kilobase pairs. Interestingly, the PARP-2 gene lies head to head with the gene encoding the mouse RNase P RNA subunit. The distance between the transcription start sites of the PARP-2 and RNase P RNA genes is 114 base pairs. This suggested that regulation of the expression of both genes may be coordinated through a bi-directional promoter. The PARP-2/RNase P RNA gene organization is conserved in the human. To our knowledge, this is the first report of a RNA polymerase II gene and an RNA polymerase III gene sharing the same promoter region and potentially the same transcriptional control elements. Reporter gene constructs showed that the 113-base pair intergenic region was indeed sufficient for the expression of both genes and revealed the importance of both the TATA and the DSE/Oct-1 expression control elements for the PARP-2 gene transcription. The expression of both genes is clearly independently regulated. PARP-2 is expressed only in certain tissues, and RNase P RNA is expressed in all tissues. This suggests that both genes may be subjected to multiple levels of control and may be regulated by different factors in different cellular contexts.Poly(ADP-ribosylation) is an immediate post-translational modification of nuclear proteins induced by DNA-damaging agents. At a site of breakage, the enzyme poly(ADP-ribose) polymerase 1 (PARP-1, 1 113 kDa) catalyzes the transfer of the ADP-ribose moiety from the respiratory coenzyme NAD ϩ to a limited number of protein acceptors involved in chromatin architecture (histones H1, H2B, lamin B, and high mobility group [HMG] proteins) or in DNA metabolism (DNA replication factors, topoisomerases including PARP-1) (1-3). Auto-and heteromodification of these proteins are part of an obligatory step of a detection/signaling pathway leading ultimately to the resolution of strand interruptions. A variety of molecular and genetic approaches have been developed this last decade that define unambiguously a critical role of PARP-1 in the cell response to DNA damage and repair and in cell death during the inflammatory process (for review, see Shall and de Murcia (4, 5)).Although it was assumed for many years that PARP activity was associated with a single protein (now termed PARP-1) displaying unique DNA damage detection properties, the recent discovery of four members of the PARP family has emphasized an unexpected complexity of poly(ADP-ribosylation) reactions in mammalian cells. We have recently cloned the cDNAs encoding human and murine PARP-2 (62 kDa), which catalyzes the formation of ADP-ribose polymers in a DNA damage-dependent manner (6). Of the three other PARP homologues that have been cloned, ...

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Section: Discussionmentioning

confidence: 99%

A Bidirectional Promoter Connects the Poly(ADP-ribose) Polymerase 2 (PARP-2) Gene to the Gene for RNase P RNA

Amé

Schreiber

Fraulob

et al. 2001

Journal of Biological Chemistry

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“…Genomic cloning has revealed that neutrophil elastase, proteinase 3, and azurocidin genes form a cluster of genes, located in the terminal region of the short arm of chromosome 19 and coordinately regulated in the promonocytic cell line U937 during induced terminal differentiation (Sturrock et al, 1992;Zimmer et al, 1992). The gene of cathepsin G belongs to another cluster of genes encoding hematopoietic serine proteases along with granzyme H and granzyme B genes on chromosome 14q11.2 (Haddad et al, 1991;Hanson et al, 1990).…”

Section: Granule Proteinsmentioning

confidence: 99%

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Witko‐Sarsat

Rieu

Descamps‐Latscha

et al. 2000

Laboratory Investigation

945

723

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“…Although both species have Gzms A and K in tightly linked clusters, 20 the genes linked with GzmB are different in the 2 species. In the human GzmB cluster, GzmB lies upstream of granzyme H (GzmH), 21 which has chymase specificity. 22 The mouse GzmB cluster is more complex.…”

Section: Introductionmentioning

confidence: 99%

Cell death induced by granzyme C

Johnson

Scorrano

Korsmeyer

et al. 2003

Blood

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Although the functions of granzymes A and B have been defined, the functions of the other highly expressed granzymes (Gzms) of murine cytotoxic lymphocytes (C, D, and F) have not yet been evaluated. In this report, we describe the ability of murine GzmC (which is most closely related to human granzyme H) to cause cell death. The induction of death requires its protease activity and is characterized by the rapid externalization of phosphatidylserine, nuclear condensation and collapse, and single-stranded DNA nicking. The kinetics of these events are similar to those caused by granzyme B, and its potency (defined on a molar basis) is also equivalent. The induction of death did not involve the activation of caspases, the cleavage of BID, or the activation of the CAD nuclease. However, granzyme C did cause rapid mitochondrial swelling and depolarization in intact cells or in isolated mitochondria, and this mitochondrial damage was not prevented by cyclosporin A pretreatment. These results suggest that granzyme C rapidly induces target cell death by attacking nuclear and mitochondrial targets and that these targets are distinct from those used by granzyme B to cause classical apoptosis. IntroductionAlthough a large number of granzyme (Gzm) genes have been identified in the mouse (A, B, C, D, E, F, G, K, and M), 1 the functions of only 2 of these enzymes (GzmA and GzmB) have been clearly defined. [2][3][4] When either GzmA or GzmB is introduced into target cells with perforin, cell death is induced. 5,6 However, the critical cellular substrates for these 2 enzymes are clearly different. Granzyme B (GzmB) is an aspase, 7,8 and it is known to cleave and activate several caspases immediately upon target cell entry, including caspase-3 and -8. 2 GzmB also cleaves ICAD, which leads to the activation of caspase-activated DNase (CAD). 9,10 Finally, GzmB is known to cleave and activate BID, which translocates to the mitochondria and facilitates the organization of a mitochondrial pore created by BAX, BAK, or both, which is followed by cytochrome c (cyt c) release and apoptosome assembly. [11][12][13][14][15][16] GzmB can also induce rapid mitochondrial depolarization independently of BAX and BAK, in cooperation with an unknown cellular factor. 16 Granzyme A (GzmA), on the other hand, is a tryptase, and its known substrates include histone H1, 17 nuclear lamins, 18 and SET, a nucleosome assembly protein that is part of a large endoplasmic reticulum-associated complex. 19 The precise contributions of these substrates to GzmA-induced cell death are not yet clear.Mice have more granzyme genes than humans. Although both species have Gzms A and K in tightly linked clusters, 20 the genes linked with GzmB are different in the 2 species. In the human GzmB cluster, GzmB lies upstream of granzyme H (GzmH), 21 which has chymase specificity. 22 The mouse GzmB cluster is more complex. The GzmB gene lies upstream from Gzms C, F, G, D, and E (5Ј 3 3Ј). 23 All the genes are in the same transcriptional orientation, and all are expressed in cy...

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A cluster of hematopoietic serine protease genes is found on the same chromosomal band as the human alpha/delta T-cell receptor locus.

Cited by 56 publications

References 37 publications

A Bidirectional Promoter Connects the Poly(ADP-ribose) Polymerase 2 (PARP-2) Gene to the Gene for RNase P RNA

A Bidirectional Promoter Connects the Poly(ADP-ribose) Polymerase 2 (PARP-2) Gene to the Gene for RNase P RNA

Neutrophils: Molecules, Functions and Pathophysiological Aspects

Cell death induced by granzyme C

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