Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases

Quesada, Vı́ctor; Díaz‐Perales, Araceli; Gutiérrez‐Fernández, Ana; Garabaya, Cecilia; Cal, Santiago; López-Otı́n, Carlos

doi:10.1016/j.bbrc.2003.12.050

Cited by 205 publications

(226 citation statements)

References 53 publications

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“…In the present study, we describe a novel and cytogenetically cryptic t(7;21)(p22;q22) in AML, fusing RUNX1 with the ubiquitinspecific protease (USP) gene USP42, which is involved in the ubiquitin pathway. 17 This is the second cryptic RUNX1 translocation described in hematologic malignancies, and the first in AML. It is also the first report of a fusion involving a USP gene in hematologic malignancies.…”

Section: Introductionmentioning

confidence: 97%

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42

et al. 2005

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Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3 0 RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected -neither on the transcriptional nor on the genomic level -and FISH showed that the 5 0 part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1 Mb proximal to USP42 and 3 Mb proximal to RUNX1; these may be important in the genesis of t (7;21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7;21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.

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Section: Introductionmentioning

confidence: 97%

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42

et al. 2005

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“…The USPs constitute the largest DUB family described to date, with >50 members (Quesada et al, 2004). All of them have highly conserved USP domains formed by three subdomains resembling the palm, thumb and fingers of a right hand (Hu et al, 2002).…”

Section: The Large and Complex Group Of Dubsmentioning

confidence: 99%

“…Furthermore, many USPs exhibit additional domains and terminal extensions that have important roles in their activity and specificity. These domains include the B-box domain found in CYLD, the zinc-finger USP domain shared by USP3, USP5, USP39, USP44, USP45, USP49 and USP51, the ubiquitin-interacting motif located in USP25 and USP37, the ubiquitin-associated domain in USP5 and USP13, the domain in USPs (DUSP) present in USP4, USP11, USP15, USP20, USP33 and USP48, the exonuclease III domain found in USP52, as well as the ubiquitin-like domain that can be located both within and outside the catalytic domains of several USPs, such as USP4, USP7, USP14, USP32, USP47 and USP48 (Quesada et al, 2004;Zhu et al, 2007b;Komander et al, 2009a) (Figure 1). Despite their relative structural diversity, most USPs share the common feature of undergoing conformational changes upon ubiquitin binding, which drives the transition from an inactive form to a catalytically active state.…”

Section: The Large and Complex Group Of Dubsmentioning

confidence: 99%

Deubiquitinases in cancer: new functions and therapeutic options

et al. 2011

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Deubiquitinases (DUBs) have fundamental roles in the ubiquitin system through their ability to specifically deconjugate ubiquitin from targeted proteins. The human genome encodes at least 98 DUBs, which can be grouped into 6 families, reflecting the need for specificity in their function. The activity of these enzymes affects the turnover rate, activation, recycling and localization of multiple proteins, which in turn is essential for cell homeostasis, protein stability and a wide range of signaling pathways. Consistent with this, altered DUB function has been related to several diseases, including cancer. Thus, multiple DUBs have been classified as oncogenes or tumor suppressors because of their regulatory functions on the activity of other proteins involved in tumor development. Therefore, recent studies have focused on pharmacological intervention on DUB activity as a rationale to search for novel anticancer drugs. This strategy may benefit from our current knowledge of the physiological regulatory mechanisms of these enzymes and the fact that growth of several tumors depends on the normal activity of certain DUBs. Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer.

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“…USP44 is located at 12q22 and encodes a 712 amino acid protein, USP44, a member of the ubiquitin-specific protease (USP) family that shows deubiquitylating activity (1,2). USP44 is an important regulator of the mitotic checkpoint by regulation of centrosome separation, positioning and mitotic spindle geometry (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…In humans, only tests showed detectable USP44 RNA amount by Northern Blot analysis and the mRNA was not detected in other organs such as ovary, colon, liver, lung, brain and kidney (1), but USP44 mRNA expression levels are reduced in human lung adenocarcinomas and the reduced level correlates with poor prognosis (5). The role of USP44 is better defined in mouse, where USP44 mRNA was detected by in situ hybridization and RT-PCR in all organs (2).…”

Section: Introductionmentioning

confidence: 99%

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

et al. 2017

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Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that plays a regulatory role in the mitotic checkpoint and USP44 loss causes chromosome missegregation, aneuploidy and tumorigenesis in vivo. In this study, it was investigated the immunoexpression of USP44 in 28 malignant salivary gland neoplasms and associated the results with DNA ploidy status assessed by image cytometry. USP44 protein was widely expressed in most of the tumor samples and no clear association could be established between its expression and DNA ploidy status or tumor size. On this basis, it may be concluded that the aneuploidy of the salivary gland cancers included in this study was not driven by loss of USP44 protein expression.

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Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases

Cited by 205 publications

References 53 publications

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42

Deubiquitinases in cancer: new functions and therapeutic options

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

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