Disease relevance of Hip1

• In this study we report that three different mutations of murine Hip1 lead to hematopoietic abnormalities reflected by diminished early progenitor frequencies and resistance to 5-FU-induced bone marrow toxicity [1].
• Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1+/- mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively [2].
• HIP1(-/-) mice develop a neurological phenotype by 3 months of age manifest with a failure to thrive, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis accompanied by decreased assembly of endocytic protein complexes on liposomal membranes [3].
• Huntingtin Interacting Protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts [1].
• Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer [4].

Psychiatry related information on Hip1

• It was reported that Hippi, when complexed with Hip1, induces the apoptosis in striatal neurons and may cause Huntington's disease [5].

High impact information on Hip1

• Feedback control of mammalian Hedgehog signaling by the Hedgehog-binding protein, Hip1, modulates Fgf signaling during branching morphogenesis of the lung [6].
• This heterodimer can recruit procaspase-8 into a complex of Hippi, Hip-1 and procaspase-8, and launch apoptosis through components of the 'extrinsic' cell-death pathway [7].
• Binding of Hip-1, a protein normally associated with Htt, is reduced by polyglutamine expansion [7].
• Together, these data provide strong evidence that HIP1 regulates AMPA receptor trafficking in the central nervous system through its function in clathrin-mediated endocytosis [3].
• In primary hippocampal neurons, HIP1 colocalizes with GluR1-containing AMPA receptors and becomes concentrated in cell bodies following AMPA stimulation [3].

Biological context of Hip1

• Here we show that these regulatory residues and others in the conserved sequence mediate light chain interaction with Hip1 and Hip1R [8].
• Huntingtin interacting protein 1 Is a clathrin coat binding protein required for differentiation of late spermatogenic progenitors [9].
• 2. In this paper we demonstrate the localization of the HIP1 mouse homologue (Hip1) into a previously identified region of human-mouse synteny on distal mouse Chromosome (Chr) 5, both employing an IRS-PCR-based mapping strategy and traditional fluorescent in situ hybridization (FISH) mapping [10].
• Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis [11].
• Using this HIP1 preparation, we have identified specific positions within the binding site that are critical for efficient protein-DNA interactions [12].

Anatomical context of Hip1

• Structural abnormalities in spermatids together with reduced sperm counts and motility underlie the reproductive defect in HIP1(-/-) mice [13].
• High levels of HIP1 protein were expressed in the testis of wild-type mice as seen by Western blots and as a reaction over Sertoli cells and elongating spermatids as visualized by immunocytochemistry [13].
• Huntingtin interacting protein 1 (HIP1) is a recently identified component of clathrin-coated vesicles that plays a role in clathrin-mediated endocytosis [3].
• Huntingtin Interacting Protein 1 (HIP1) binds clathrin and AP2, is overexpressed in multiple human tumors, and transforms fibroblasts [1].
• Postmeiotic spermatids are the only cells of the seminiferous tubules that express HIP1 [9].

Associations of Hip1 with chemical compounds

• INTERPRETATION AND CONCLUSIONS: Although imatinib represents an attractive therapeutic agent for neoplasias associated with abnormal PDGFRbeta signaling, the low frequency of the TEL/PDGFRbeta and Hip1/PDGFRbeta fusion proteins in CMML suggests that its application to this disease maybe limited [14].
• Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer [11].
• Results suggest that the transport of huntingtin and its co-expression in clathrin and huntingtin-interacting protein 1-enriched membranes is influenced by activation of adenylyl cyclase and stimulation of dopamine D1 receptors [15].

Other interactions of Hip1

• Moreover, a profound dose-dependent defect in clathrin-mediated internalization of GluR1-containing AMPA receptors was observed in neurons from HIP1(-/-) mice [3].
• Huntingtin-associated protein 1 (Hap1) is the first huntingtin interacting protein identified in a yeast two-hybrid screen [16].

Analytical, diagnostic and therapeutic context of Hip1

• Quantitative analyses of sperm counts from the cauda epididymidis demonstrated a significant decrease in HIP1(-/-) mice compared to wild-type littermates [13].
• Immunoblot analysis of subcellular membrane fractions separated by differential centrifugation confirmed that huntingtin immunoreactivity in differentiated neurons markedly increased in membrane fractions enriched with clathrin and with huntingtin-interacting protein 1 [15].

References