Huntingtin-interacting protein 1

Last updated
HIP1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HIP1 , HIP-I, ILWEQ, SHON, SHONbeta, SHONgamma, huntingtin interacting protein 1
External IDs OMIM: 601767 MGI: 1099804 HomoloGene: 68463 GeneCards: HIP1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001243198
NM_005338
NM_001382444
NM_001382445

NM_146001
NM_001382848

RefSeq (protein)

NP_001230127
NP_005329
NP_001369373
NP_001369374

NP_666113
NP_001369777

Location (UCSC) Chr 7: 75.53 – 75.74 Mb Chr 5: 135.41 – 135.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Huntingtin-interacting protein 1 also known as HIP-1 is a protein that in humans is encoded by the HIP1 gene.

Contents

Hip-1 is a protein that interacts with the huntingtin protein. It is known to contain a domain homologous to the death effector domains (DED) found on proteins involved in apoptosis. It is believed that accumulation of high levels of the free form of this protein (free as in dissociated from the huntingtin and free to bind other key protein(s)) in the cell is one of the mechanisms by which neuron cell death is caused in Huntington's disease (via the caspase-3 route). The role of Hip-1 in caspase mediated cell death remains unclear.

Discovery

Huntingtin interacting protein 1 (HIP1) was first identified by Wanker et al. in 1997. [5]

Function

HIP1 was found to bind to Htt in an N-terminal dependent manner, and co-localise with Htt in the CNS although the nature of this interaction with respect to muHtt was not identified. It has since been found that the CAG expansion seen with muHtt results in decreased binding affinity for HIP1, thus causing disruption of HIP1’s usual function, and also an increase in free HIP1. [6] It is likely that this decreased affinity plays a role in mediating HD pathogenesis, due to loss of cytoskeletal integrity and induction of apoptosis. HIP1’s pro apoptotic effect may involve activation of caspase-8 and a novel HIP1 protein interactor HIPPI. [7] HIP1’s non-pathological activity includes clathrin assembly via interaction with clathrin light chains. [8] HIP1 is the human homologue of Sla2p, a membrane protein in the periphery. [9] Sla2p is an actin-binding protein involved in endocytosis, thus indicating HIP1 in this role. Further details suggesting an important role for Hip-1 in endocytosis comes from binding studies looking at Hip-1 binding to actin. Actin binding by Hip-1 is altered depending on whether clathrin is also bound to Hip-1.

Clinical significance

HIP1 has also been found to be overexpressed in some cancers including a subset of colorectal and prostate cancers. [10] This is of specific interest because prostate cancer disease progression involves altered transcription/expression of the androgen receptor (AR). [11] The AR is a nuclear hormone receptor transcription factor that contains polyglutamine repeats. In 2005 Mills and colleagues showed that HIP1 is able to regulate transcription of hormone receptors via the androgen response element (ARE) and also alters the rate of degradation of the AR. [12] It is likely that HIP1 is also able to regulate, or at least interact with proteins that also possess the ARE.

Related Research Articles

<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in Homo sapiens

The androgen receptor (AR), also known as NR3C4, is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.

<span class="mw-page-title-main">Death effector domain</span> InterPro Domain

The death-effector domain (DED) is a protein interaction domain found only in eukaryotes that regulates a variety of cellular signalling pathways. The DED domain is found in inactive procaspases and proteins that regulate caspase activation in the apoptosis cascade such as FAS-associating death domain-containing protein (FADD). FADD recruits procaspase 8 and procaspase 10 into a death induced signaling complex (DISC). This recruitment is mediated by a homotypic interaction between the procaspase DED and a second DED that is death effector domain in an adaptor protein that is directly associated with activated TNF receptors. Complex formation allows proteolytic activation of procaspase into the active caspase form which results in the initiation of apoptosis. Structurally the DED domain are a subclass of protein motif known as the death fold and contains 6 alpha helices, that closely resemble the structure of the Death domain (DD).

<span class="mw-page-title-main">TRAIL</span>

In the field of cell biology, TNF-related apoptosis-inducing ligand (TRAIL), is a protein functioning as a ligand that induces the process of cell death called apoptosis.

<span class="mw-page-title-main">Huntingtin</span> Gene and protein involved in Huntingtons disease

Huntingtin(Htt) is the protein coded for in humans by the HTT gene, also known as the IT15 ("interesting transcript 15") gene. Mutated HTT is the cause of Huntington's disease (HD), and has been investigated for this role and also for its involvement in long-term memory storage.

<span class="mw-page-title-main">Low-affinity nerve growth factor receptor</span> Human protein-coding gene

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<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Protein-coding gene in the species Homo sapiens

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

<span class="mw-page-title-main">CREB-binding protein</span> Nuclear protein that binds to CREB

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<span class="mw-page-title-main">Caspase 8</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">XIAP</span> Protein-coding gene in the species Homo sapiens

X-linked inhibitor of apoptosis protein (XIAP), also known as inhibitor of apoptosis protein 3 (IAP3) and baculoviral IAP repeat-containing protein 4 (BIRC4), is a protein that stops apoptotic cell death. In humans, this protein (XIAP) is produced by a gene named XIAP gene located on the X chromosome.

Huntingtin-associated protein 1 (HAP1) is a protein which in humans is encoded by the HAP1 gene. This protein was found to bind to the mutant huntingtin protein (mHtt) in proportion to the number of glutamines present in the glutamine repeat region.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

<span class="mw-page-title-main">HCLS1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TRIP10</span> Protein-coding gene in the species Homo sapiens

Cdc42-interacting protein 4 is a protein that in humans is encoded by the TRIP10 gene.

<span class="mw-page-title-main">DLC1</span> Protein-coding gene in the species Homo sapiens

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

<span class="mw-page-title-main">KAT7 (gene)</span> Protein-coding gene in the species Homo sapiens

Histone acetyltransferase KAT7 is an enzyme that in humans is encoded by the KAT7 gene. It specifically acetylates H4 histones at the lysine12 residue (H4K12) and is necessary for origin licensing and DNA replication. KAT7 associates with origins of replication during G1 phase of the cell cycle through complexing with CDT1. Geminin is thought to inhibit the acetyltransferase activity of KAT7 when KAT7 and CDT1 are complexed together.

<span class="mw-page-title-main">GTF3A</span> Protein-coding gene in the species Homo sapiens

Transcription factor IIIA is a protein that in humans is encoded by the GTF3A gene. It was first isolated and characterized by Wolffe and Brown in 1988.

<span class="mw-page-title-main">CASP8AP2</span> Protein-coding gene in the species Homo sapiens

CASP8-associated protein 2 is a protein, that in humans is encoded by the CASP8AP2 gene.

<span class="mw-page-title-main">HIP1R</span>

Huntingtin-interacting protein 1-related protein is a protein that in humans is encoded by the HIP1R gene.

<span class="mw-page-title-main">IFT57</span> Protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000127946 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039959 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Wälter S, Tait D, Colicelli J, Lehrach H (Mar 1997). "HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system". Human Molecular Genetics. 6 (3): 487–95. doi: 10.1093/hmg/6.3.487 . PMID   9147654.
  6. Hackam AS, Yassa AS, Singaraja R, Metzler M, Gutekunst CA, Gan L, Warby S, Wellington CL, Vaillancourt J, Chen N, Gervais FG, Raymond L, Nicholson DW, Hayden MR (Dec 2000). "Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain". The Journal of Biological Chemistry. 275 (52): 41299–308. doi: 10.1074/jbc.M008408200 . PMID   11007801.
  7. Gervais FG, Singaraja R, Xanthoudakis S, Gutekunst CA, Leavitt BR, Metzler M, Hackam AS, Tam J, Vaillancourt JP, Houtzager V, Rasper DM, Roy S, Hayden MR, Nicholson DW (Feb 2002). "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nature Cell Biology. 4 (2): 95–105. doi:10.1038/ncb735. PMID   11788820. S2CID   10439592.
  8. Legendre-Guillemin V, Metzler M, Lemaire JF, Philie J, Gan L, Hayden MR, McPherson PS (Feb 2005). "Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain". The Journal of Biological Chemistry. 280 (7): 6101–8. doi: 10.1074/jbc.M408430200 . PMID   15533941.
  9. Holzmann C, Schmidt T, Thiel G, Epplen JT, Riess O (Aug 2001). "Functional characterization of the human Huntington's disease gene promoter". Brain Research. Molecular Brain Research. 92 (1–2): 85–97. doi:10.1016/s0169-328x(01)00149-8. PMID   11483245.
  10. Rao DS, Hyun TS, Kumar PD, Mizukami IF, Rubin MA, Lucas PC, Sanda MG, Ross TS (Aug 2002). "Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival". The Journal of Clinical Investigation. 110 (3): 351–60. doi:10.1172/JCI15529. PMC   151092 . PMID   12163454.
  11. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, Sawyers CL (Jan 2004). "Molecular determinants of resistance to antiandrogen therapy". Nature Medicine. 10 (1): 33–9. doi:10.1038/nm972. PMID   14702632. S2CID   1182764.
  12. Mills IG, Gaughan L, Robson C, Ross T, McCracken S, Kelly J, Neal DE (Jul 2005). "Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors". The Journal of Cell Biology. 170 (2): 191–200. doi:10.1083/jcb.200503106. PMC   2171420 . PMID   16027218.