Disease relevance of Casp6

• In addition, mutant neurons showed no evidence of compensatory activation by caspase-6 or caspase-7 after ischemia [1].
• Early processing of Bid and caspase-6, -8, -10, -14 in the canine brain during cardiac arrest and resuscitation [2].
• In this study, we extend the repertoire of chimeric proapoptotic proteins with immunocasp-6, a construct that comprises a HER2-specific single-chain Ab, a single-chain Pseudomonas exotoxin A, and an active caspase-6, which can directly cleave lamin A leading to nucleus damage and inducing programmed cell death [3].

High impact information on Casp6

• Furthermore, caspase-6-resistant mutant htt mice are protected against neurotoxicity induced by multiple stressors including NMDA, quinolinic acid (QA), and staurosporine [4].
• This work provided evidence that CBP is specifically targeted by caspases and calpains at the onset of neuronal apoptosis, and CBP was futher identified as a new caspase-6 substrate [5].
• K18 is cleaved by caspase-6 into NH2-terminal, 26-kD and COOH-terminal, 22-kD fragments; caspase-3 and -7 additionally cleave the 22-kD fragment into a 19-kD fragment [6].
• Histologically, at this time there is apoptosis, but no excess deposition of collagen or glycogen. mRNA expression is elevated for caspase 1, caspase 6, and several enzymes associated with sterol biosynthesis and bile acid formation [7].
• Transcriptional profiling revealed reduced levels of caspase-6 mRNA in p85beta-deficient T cells, which was paralleled by reduced caspase-6 enzyme activity [8].

Biological context of Casp6

• On the basis of sequence homology, the caspases can be divided into three subfamilies: first, mCASP-1, mCASP-11 and mCASP-12; second, mCASP-2; third, mCASP-3, mCASP-6 and mCASP-7 [9].
• Finally, we also show that teratogen-induced activation of caspase-6 and caspase-7 are blocked in the heart, a tissue resistant to teratogen-induced cell death [10].
• These findings suggest a mechanism by which caspase-6 may selectively allow entry of quiescent B cells into the cell cycle [11].
• These proteins included growth arrest specific protein, DNA binding protein, caspase 6, pinch protein and ras-related protein rab-36, which are involved in cell cycling, transcription regulation, signaling pathways and apoptosis [12].

Anatomical context of Casp6

• Thus, caspase-6-like activity is required for quiescent B cells to increase the expression of genes required for entry into G(1) [11].
• Immunocytochemical localization of activated caspase-3 and a cleaved substrate of caspase-6 confirms that caspase activation extends into the cytosol and nucleus [13].
• Organelle degradation is accompanied by an increase in VEIDase (caspase-6-like) activity, but data from caspase-null mice suggest that the lens VEIDase is not caspase-6 [14].
• These results show that the process of programmed cell death in muscle cells leads to emerin proteolysis, which appears to be related to caspase 6 activation and to cleavage of other nuclear envelope proteins, that share sequence homologies or functional features with emerin [15].
• Cleavage of focal adhesion kinase and Lamin, substrates of caspase 6, was also evident in spontaneous II-APO [16].

Associations of Casp6 with chemical compounds

• In vivo, pilocarpine-induced seizures, previously shown to up-regulate p75 expression and increase neurotrophin production, caused activation of caspase-6 and -3 and cleavage of poly(ADP-ribose) polymerase in p75-expressing hippocampal neurons [17].
• The in vitro antiapoptotic effect of dehydroepiandrosterone sulfate in mouse thymocytes and its relation to caspase-3/caspase-6 [18].
• At the glucose level of 10 mmol/l, palmitate induced caspase-6 activity within 3 h, and caspase-3 activity after a lag period of 6 h [19].
• Increased mRNA expression of caspase 3 and caspase 6 in all-trans-retinoic acid-exposed ES cells suggested that caspases play an important role in retinoic acid-mediated apoptosis during ES differentiation [20].
• When AC-YVAD-CHO, an inhibitor of caspase 6, was introduced into the system, these vesicles and apoptotic bodies disappeared completely within our study sections [21].

Enzymatic interactions of Casp6

• The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis [22].

Regulatory relationships of Casp6

• In addition, caspase-6 could be activated by the addition of either recombinant caspase-3 or caspase-9 to a lysate prepared from untreated embryos [10].
• The caspase-6 inhibitor Z-Val-Glu(OMe)-Ile-Asp(OMe)-CH(2)F potently suppressed Akt ubiquitination, degradation, and fragment formation, whereas the proteasome inhibitor Z-Leu-Leu-Leu-CHO modestly attenuated the decline in Akt levels [23].

Other interactions of Casp6

• Additionally, cleavage data reveal not only proteolytic amplification between caspase-3 and -8, caspase-6 and -3, and caspase-6 and -7, but also positive feedback loops involving multiple activated caspases [24].
• A time-course study indicated that activation of caspase-2 and -8 occurred upstream of caspase-6 and caspase-7 [25].
• In vitro studies showed that both caspase-6 and caspase-7 could be activated by the addition of cytochrome c to a lysate prepared from untreated embryos [10].
• Proliferation was blocked by either a broad specificity caspase inhibitor or inhibitors selective for caspase-6 or caspase-8 [11].
• The ability of PUMA to induce apoptosis was greater than that of caspase-6 or caspase-8 transfer, using the same system [26].

Analytical, diagnostic and therapeutic context of Casp6

• Transcripts for all three executioner caspases were identified in lens fiber cells by real time RT-PCR, although only caspase-6 and -7 proteins were detected subsequently by Western blot analysis [27].
• Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration [28].
• In the course of apoptosis, caspase-3-like activity increased first at 75 min, simultaneously with the appearance of TUNEL staining and prior to PARP cleavage, and then caspase-6 and 8-like activities increased at 90 and 105 min, respectively [29].

References