Disease relevance of CLP1

• We have recently cloned a human cDNA (hClpP) with significant sequence similarity to the ATP-dependent Escherichia coli ClpP protease [Bross, Andresen, Knudsen, Kruse and Gregersen (1995) FEBS Lett. 377, 249-252] [1].

High impact information on CLP1

• Antibodies directed against hClp1 deplete cleavage activity, but not polyadenylation activity from HeLa cell nuclear extract. hClp1 interacts with CF I(m) and the cleavage and polyadenylation specificity factor CPSF, suggesting that it bridges these two 3' end processing factors within the cleavage complex [2].
• AF10 is split by MLL and HEAB, a human homolog to a putative Caenorhabditis elegans ATP/GTP-binding protein in an invins(10;11)(p12;q23q12) [3].
• HEAB protein shows high homology in its entire amino acid sequence to a putative C elegans protein and contains an adenosine triphosphate (ATP)/guanosine triphosphate (GTP)-binding motif that has homology to the ATP-binding transporter superfamily or to GTP-binding proteins [3].
• The HEAB gene encodes a 425-amino acid protein that is rich in valine and leucine [3].
• Northern blot analysis of HEAB expression shows that a 2.0-kb major transcript is expressed ubiquitously in human tissues and is especially abundant in testis and skeletal muscle, whereas a 3.2-kb minor transcript is noted with the highest level of expression in thymus and peripheral blood leukocytes [3].

Biological context of CLP1

• The hClpXP complex has protease activity and greatly increased peptidase activity, indicating that interaction with hClpX affects the conformation of the hClpP catalytic active site [4].
• Taken together, the results reported here show that hClpP is localized inside mitochondria and that the trafficking and processing of hClpP resembles the typical biogenesis pathway for nuclear-encoded mitochondrial proteins [1].
• The validity of our approach is exemplified by the sequence analysis of a 597-bp cDNA clone, designated CLP-1, that contains a 390-bp open reading frame (ORF) flanked by motifs characteristic to a full-length cDNA [5].

Anatomical context of CLP1

• These data suggest that hClpX can regulate the appearance of hClpP peptidase activity in mitochondria and might affect the nature of the degradation products released during ATP-dependent proteolytic cycles [4].
• The processing of hClpP in intact cells was dependent on mitochondrial membrane potential [1].
• In the present study, synthesis, intracellular processing and subcellular localization of hClpP have been analysed in intact cells and in a cell-free system [1].
• These results were confirmed in an import assay system using in vitro transcription and translation directed by the hClpP cDNA and isolated rat liver mitochondria [1].
• Thus, Gfi1 selectively specifies IL7-dependent development of B cells from CLP1 progenitors, providing clues to the transcriptional networks integrating cytokine signals and lymphoid differentiation [6].

Associations of CLP1 with chemical compounds

• A mutant of hClpP, in which a cysteine residue was introduced into the handle region at the interface between the two rings formed stable tetradecamers under oxidizing conditions but spontaneously dissociated into two heptamers upon reduction [4].
• The relative abundance of the CLP-1 message in the labial palps of females leads to the suggestion that this protein is involved in the CO2-sensing cascade [5].

Analytical, diagnostic and therapeutic context of CLP1

• Electron microscopy confirmed that hClpP forms heptameric rings and that hClpX forms a hexameric ring [7].
• Using pulse-labelling/immunoprecipitation of Chang cells transfected with the hClpP cDNA, we observed two major bands with apparent molecular masses of approx. 39 and 37 kDa [1].

References