<i>Leishmania donovani</i>cyclin 1 (LdCyc1) forms a complex with cell cycle kinase subunit CRK3 (LdCRK3) and is possibly involved in S-phase-related activities

Banerjee, Sampali; Sen, Abhik; Das, Pradeep; Saha, Partha

doi:10.1111/j.1574-6968.2006.00105.x

Cited by 23 publications

(22 citation statements)

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“…The mRNA of S-phase cyclin LdCyc1 of L. donovani was found to contain a single copy of the conserved octamer sequence in its 5 0 -UTR [13,14], and in the present study, RNA electrophoretic mobility shift assay (REMSA) was performed to determine whether LdCSBP interacts with the UTR specifically. The slower moving bands in REMSA with the extract of Sf9 insect cell expressing LdCSBP and a 32 P-labeled RNA probe containing the 5 0 -UTR of LdCyc1 (Fig.…”

Section: Ldcsbp Interacts Specifically With Utr Of An S-phase Mrna Thmentioning

confidence: 94%

Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain

et al. 2011

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Edited by Michael IbbaKeywords: CCCH Zn-finger mRNA turnover Smr domain RNA endonuclease Ubiquitination Leishmania donovani a b s t r a c tIn trypanosomatid parasites, an octanucleotide sequence (C/A)AUAGAA(G/A) in the UTRs primarily determines the stability of S-phase specific mRNAs. A multi-domain protein LdCSBP from Leishmania donovani interacts with the UTR of an S-phase RNA containing the octanucleotide sequence through its unique CCCH-type Zn-finger motifs. Interestingly, the RNA binding protein contains a previously characterized DNA endonuclease domain -Smr. It has been demonstrated here that the LdCSBP Smr domain independently possesses both DNA and RNA endonuclease activities, but the full-length LdCSBP exhibits only riboendonuclease activity. Moreover, LdCSBP protein has been shown to be ubiquitinated, resulting in the down-regulation of its riboendonuclease activity. In conclusion, the results described here suggest a novel regulatory mechanism of mRNA degradation through ubiquitination in eukaryotes.

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Section: Ldcsbp Interacts Specifically With Utr Of An S-phase Mrna Thmentioning

confidence: 94%

Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain

et al. 2011

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“…Trypanosomatid CDKs contain cyclin-binding regions as anticipated (Naula et al 2005 ), whereas the presence of a cyclin (CYC2, CYC3, CYC6 for T . brucei , and CYC1, CYCA and CYC6 for Leishmania ) for the activity of the trypanosomatid homologue of mammalian CDK1 (CRK3) has been shown (Wang et al 1998 ;Van Hellemond et al 2000 ;Li and Wang 2003 ;Hammarton et al 2003Hammarton et al , 2004Tu and Wang 2004 ;Banerjee et al 2006 ;Gomes et al 2010 ). The function of two kinases from L .…”

Section: Kinasesmentioning

confidence: 99%

Selection of Molecular Targets for Drug Development Against Trypanosomatids

Smirlis

Soares

2013

Subcellular Biochemistry

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Trypanosomatid parasites are a group of flagellated protozoa that includes the genera Leishmania and Trypanosoma, which are the causative agents of diseases (leishmaniases, sleeping sickness and Chagas disease) that cause considerable morbidity and mortality, affecting more than 27 million people worldwide. Today no effective vaccines for the prevention of these diseases exist, whereas current chemotherapy is ineffective, mainly due to toxic side effects of current drugs and to the emergence of drug resistance and lack of cost effectiveness. For these reasons, rational drug design and the search of good candidate drug targets is of prime importance. The search for drug targets requires a multidisciplinary approach. To this end, the completion of the genome project of many trypanosomatid species gives a vast amount of new information that can be exploited for the identification of good drug candidates with a prediction of "druggability" and divergence from mammalian host proteins. In addition, an important aspect in the search for good drug targets is the "target identification" and evaluation in a biological pathway, as well as the essentiality of the gene in the mammalian stage of the parasite, which is provided by basic research and genetic and proteomic approaches. In this chapter we will discuss how these bioinformatic tools and experimental evaluations can be integrated for the selection of candidate drug targets, and give examples of metabolic and signaling pathways in the parasitic protozoa that can be exploited for rational drug design.

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“…The purified proteins could also be phosphorylated in a Cy-motif dependent manner by LdCyc1 associated kinase (Fig. 2C) isolated from L. donovani promastigote extract through anti-LdCyc1 immunoprecipitation [10], suggesting the proteins could be the authentic in vivo substrates.…”

Section: The In Vitro Expressed Proteins Act As Substrates Of Ldcyc1/mentioning

confidence: 99%

“…It was also observed that the specificity of Clb5-Cdc28 of budding yeast in S-phase primarily depends on the substrate RXL motif [14]. Therefore, in order to identify the potential substrates of S-phase cell cycle kinase LdCyc1/CRK3 from Leishmania [9,10], 28 putative ORFs containing both the conserved Cy-motif and the Cdk phosphorylation site were selected from the genome database of L. major for screening. The ORFs which were larger than 3 kb in length and/or A B contained putative trans-membrane domain were not included in the present studies to avoid the difficulties of amplification of large templates from the GC-rich genome and insolubility of the expressed proteins, respectively.…”

Section: Three Proteins Containing Both Cy-motif and Cdk Phosphorylatmentioning

confidence: 99%

“…LdCyc1 [9,10] contains the conserved substrate docking MRAIL-like motif, which is also found in other cyclins and responsible for the interaction with consensus RRL-like cyclin binding (Cy) motif present on the target proteins. The Cy-motif was first identified in the cyclin-Cdk inhibitor p21 [11], and later found to be present in other inhibitors (p27 and p57), activator Cdc25A [12] and substrates Rb, Cdc6 and others [1,3].…”

Section: Introductionmentioning

confidence: 99%

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Identification of substrates of an S-phase cell cycle kinase fromLeishmania donovani

2011

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Edited by Michael IbbaKeywords: Cyclin-Cdk substrate Cdk related kinase Cyclin binding motif Cell cycle Leishmania donovani a b s t r a c t Despite the importance of cyclin-Cdk related kinases (CRK) in regulation of cell and life cycle of kinetoplastida parasites, only limited knowledge about their substrates are presently available. Here, the potential substrates were searched for an S-phase LdCyc1-CRK3 complex from Leishmania donovani based on the presence of Cdk target phosphorylation site together with the cyclin interacting Cy-motif in genome-derived putative protein sequences. Three substrates could be identified with one of them being a unique protein with no known homologues. Another identified substrate is similar to MYST family of histone acetyl transferase and the third one contains Ku-70 related conserved domains. All the substrates interact directly with LdCyc1 and are phosphorylated in a Cy-motif dependent manner suggesting the importance of Cy-motif for their functions. Structured summary of protein interactions:LdCyc1 physically interacts with Ld14.0140L by pull down (View interaction). LdCyc1 physically interacts with Ld28.0070L by pull down (View interaction). LdCyc1 physically interacts with Ld29.1050L by pull down (View interaction).

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Leishmania donovanicyclin 1 (LdCyc1) forms a complex with cell cycle kinase subunit CRK3 (LdCRK3) and is possibly involved in S-phase-related activities

Cited by 23 publications

References 37 publications

Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain

Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain

Selection of Molecular Targets for Drug Development Against Trypanosomatids

Identification of substrates of an S-phase cell cycle kinase fromLeishmania donovani

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