Induction of apoptosis in cells expressing exogenous Hippi, a molecular partner of huntingtin-interacting protein Hip1

Cloning, expression, purification, crystallization and preliminary crystallographic analysis of pseudo death-effector domain of HIPPI, a molecular partner of Huntingtin-interacting protein HIP-1

“…Recently, we have shown that exogenous expression of HIPPI in Neuro2A neuronal cells increases apoptosis by activating caspase-1 and caspase-3 and releasing cytochrome c from mitochondria. We have also reported that caspase-1, caspase-8, caspase-9/caspase-6 and caspase-3 activation and nuclear fragmentation were increased significantly when HIPPI was overexpressed in HeLa and Neuro2A cells (Majumder et al, 2006).…”

“…This complex then recruits the initiator caspase-8 and activates the enzymes for apoptosis (Gervais et al, 2002;Majumder et al, 2006). This cellular model provides an alternative explanation for the increased apoptosis observed in HD and deviates slightly from the earlier model, in which aggregates formed by the mutated Htt recruit caspase-8 and initiate apoptosis (Sá nchez et al, 1999).…”

Studying neurodegenerative diseases in culture models

“…Therefore, primary neurons prepared from HD transgenic mice are frequently used: neocortical or striatal cultures from HdhQ111 mice that have 111 CAG repeats in exon 1 of the mHtt gene [115][116][117][118][119] ; neostriatal cultures of the YAC46 (668 line) and YAC72 (2511 line) mice, which express the full-length mutant huntingtin containing 46 or 72 glutamine repeats (46Q or 72Q) 120 ; YAC128 (line 55) mice expressing full-length human mHtt containing 128 CAG repeats 121 ; transgenic BACHD mice that express a fulllength mHtt with 97 glutamine repeats. 122 Besides the neuronal cells, mHtt may also be transfected to non-neuronal cells, 95 such as HeLa cells, [123][124][125][126] human embryonic kidney cell-line 293T (HEK293T), 93,123,126,127 and monkey kidney cell lines (COS-7). 107,128,129 An interesting approach has been obtained with acute transfection of rat corticostriatal brain slices with DNA constructs derived from the human mHtt.…”

Regulation of RE1 Protein Silencing Transcription Factor (REST) Expression by HIP1 Protein Interactor (HIPPI)

“…Under diseased conditions when HTT is mutated, HIP1 dissociates from mutant HTT and interacts with HIPPI, a novel pseudo-death effector domain (pDED)-containing protein. HIPPI-HIP1 heterodimer then recruits procaspase-8, followed by its activation and induction of the downstream apoptotic cascade (16,18).…”

“…While investigating the HIPPI-mediated apoptotic pathway in detail, Majumder et al (18) observed that HIPPI positively * This work was supported by the Department of Atomic Energy, Government of India. □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1 and S2 and Figs.…”