CRABP1
Identifiers
AliasesCRABP1, CRABP, CRABP-I, CRABPI, RBP5, cellular retinoic acid binding protein 1
External IDsOMIM: 180230 MGI: 88490 HomoloGene: 3222 GeneCards: CRABP1
Orthologs
SpeciesHumanMouse
Entrez

1381

12903

Ensembl

ENSG00000166426

ENSMUSG00000032291

UniProt

P29762

P62965

RefSeq (mRNA)

NM_004378

NM_001284507
NM_013496

RefSeq (protein)

NP_004369

NP_001271436
NP_038524

Location (UCSC)Chr 15: 78.34 – 78.35 MbChr 9: 54.67 – 54.68 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cellular retinoic acid-binding protein 1 is a protein that in humans is encoded by the CRABP1 gene.[5][6]

CRABP1 is assumed to play an important role in retinoic acid-mediated differentiation and proliferation processes. It is structurally similar to the cellular retinol-binding proteins, but binds only retinoic acid. CRABP1 is constitutively expressed and is believed to have different functions in the cell than the related CRABP2.[6]

Function

Figure 1. An overview of retinoid transfer by CRABP. R = Retinoic acid, RAR = retinoic acid receptor, RXR = Retinoic X receptor, RRE = retinoid response element. CRABP binds to retinoic acid and transports it to the nucleus where binding with RAR or RXR homodimers or heterodimers further regulates RREs to regulate transcription events on DNA.[7]
Figure 2. Retinoic acid (RA) is processed from vitamin A to bind to fatty acid binding protein (FABP5) along with CRABP to associate with the binding to DNA to mediate pathways. RA binds with CRABP to mediate further action with retinoic acid receptor (RAR) on DNA for pathway mediation as well.[8]
Figure 3. Image of the domain locations for CRABP1. The nuclear localization signal (NLS) is at position 21-31 and the retinoic acid binding site (RBS) is at position 132-134.[9]

CRABP1 binds to retinoid acid and helps to transport it into the nucleus (Figure 1). Both CRABP1 and CRABP2 perform this activity. The retinoic acid molecule is then released and further bound to retinoic acid receptor (RAR) and the retinoid X receptor (RXR) as homodimers or heterodimers. This complex then further binds to retinoic acid response elements (RARE) on DNA that regulates transcription of retinoid acid dependent null genes.[10] The domains for the nuclear localization and the retinoic acid binding are shown in Figure 3.

CRABP1 has been found to be involved in multiple cancer proliferation pathways. CRABP1 activates the extracellular signal-regulated kinase, ERK1 and ERK2 kinases, which are involved in the cell cycle. CRABP1 activity can thus extend the cell cycle, e.g. in embryonic and neural stem cells. Knockout mice without CRABP1 showed increased neural stem cell proliferation and thus hippocampus neurogenesis. Furthermore, learning and memory were improved in knockout mice, as measured by the Morris water maze test and an object recognition task.[11]

CRABP1 is also involved in cancer cell apoptosis. trans-retinoic acid was considered a [null therapeutic target for cancer] as a ligand of CRABP1.[12] It was observed that CRABP1 regulated ERK1/2) which in turn activates the protein phosphatase 2A (PP2A) that induces apoptosis of cancer cells and lengthens the cell cycle of embryonic stem cells. PP2A activity promotes the stem cells renewal ability during the differentiation process. When CRABP1 was knocked down the apoptotic induction ability was also removed and allowed for cell proliferation. The re-expression of CRABP1 in CRABP1 null cells brought back the induced apoptotic activity. Thus CRABP1 may be used as a therapeutic target along with trans-retinoic acid for apoptotic activity within cancer cells.[12] Figure 2 illustrates both pathways of retinoic acid binding to CRABP for cell proliferation and apoptotic activity.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000166426 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032291 - 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. ↑ Flagiello D, Apiou F, Gibaud A, Poupon MF, Dutrillaux B, Malfoy B (Jun 1997). "Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and 2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ hybridization". Cytogenetics and Cell Genetics. 76 (1–2): 17–8. doi:10.1159/000134502. PMID 9154115.
  6. 1 2 "Entrez Gene: CRABP1 cellular retinoic acid binding protein 1".
  7. ↑ Redrawn from Lee K (April 2017). "Retinol for all". The Regime.
  8. ↑ Redrawn from Michalik L, Wahli W (May 2007). "Guiding ligands to nuclear receptors". Cell. 129 (4): 649–51. doi:10.1016/j.cell.2007.05.001. PMID 17512397. S2CID 17253347.
  9. ↑ Adapted from Universal protein resource accession number P29762 for "RABP1_HUMAN" at UniProt.
  10. ↑ Liu RZ, Garcia E, Glubrecht DD, Poon HY, Mackey JR, Godbout R (July 2015). "CRABP1 is associated with a poor prognosis in breast cancer: adding to the complexity of breast cancer cell response to retinoic acid". Molecular Cancer. 14: 129. doi:10.1186/s12943-015-0380-7. PMC 4491424. PMID 26142905.
  11. ↑ Lin YL, Persaud SD, Nhieu J, Wei LN (September 2017). "Cellular Retinoic Acid-Binding Protein 1 Modulates Stem Cell Proliferation to Affect Learning and Memory in Male Mice". Endocrinology. 158 (9): 3004–3014. doi:10.1210/en.2017-00353. PMC 5659671. PMID 28911165.
  12. 1 2 Persaud SD, Park SW, Ishigami-Yuasa M, Koyano-Nakagawa N, Kagechika H, Wei LN (March 2016). "All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1/2 phosphorylation". Scientific Reports. 6: 22396. Bibcode:2016NatSR...622396P. doi:10.1038/srep22396. PMC 4776112. PMID 26935534.

Further reading

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