Cerberus (protein)

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Cerberus 1, DAN family BMP antagonist
Identifiers
Symbols CER1 ; DAND4
External IDs OMIM603777 MGI1201414 HomoloGene3983 GeneCards: CER1 Gene
Orthologs
Species Human Mouse
Entrez 9350 12622
Ensembl ENSG00000147869 ENSMUSG00000038192
UniProt O95813 O55233
RefSeq (mRNA) NM_005454 NM_009887
RefSeq (protein) NP_005445 NP_034017
Location (UCSC) Chr 9:
14.72 – 14.72 Mb
Chr 4:
82.88 – 82.89 Mb
PubMed search [1] [2]

Cerberus also known as CER1 is a protein that in humans is encoded by the CER1 gene.[1][2]

Function[edit]

Cerberus is an inhibitor in the TGF beta signaling pathway secreted during the gastrulation phase of the embryogenesis. Cerberus (Cer) is a gene that encodes a cytokine (a secreted signaling protein) important for the induction of head formation of vertebrates.[3] The Cerberus gene encodes a polypeptide that is 270 amino acids in length and is expressed in the anterior domain of a gastrula in the endoderm layer.[4] Cerberus also plays a large role as an inhibitory molecule, which is important for proper head induction. Cerberus inhibits the proteins BMP4, Xnr1, and Xwnt8.

This gene encodes a cytokine member of the cystine knot superfamily, characterized by nine conserved cysteines and a cysteine knot region. The cerberus-related cytokines, together with Dan and DRM / Gremlin, represent a group of bone morphogenetic protein (BMP) antagonists that can bind directly to BMPs and inhibit their activity.[1]

In human embryonic development, Cerberus and the protein coded by GREM3 inhibit Nodal in the Wnt signaling pathway during the formation of the germ layers. Specifically, Cerberus and GREM3 act as antagonists to Nodal in the anterior region of the developing embryo, blocking its expression and halting the progression of the primitive node. Orthologs of the gene that codes Cerberus (CER1) are conserved in other non-rodent mammals, indicating that Cerberus has similar functions in other vertebrates.[5]

A Gene knock down experiment was conducted in Xenopus where the amount of Cerberus expressed was decreased by inhibiting translation. The proteins that Cerberus inhibits (BMP4, Xnr1, Xwnt8) concentrations were increased also. It was also shown that just the decrease of Cerberus translation alone was not enough to inhibit the formation of head structures. While the increase of just BMP4, Xnr1, Xwnt8 led to defects in the formation of the head. The increase of BMP4, Xnr1, Xwnt8 and the decrease of Cerberus together blocked the formation of the head. This gene knockdown experiment showed the necessity of Cerberus’ inhibitory functions in the formation of head structures. It quite possibly may be that although Cerberus is necessary for the induction of a head, its inhibitory actions may play a more significant role in ensuring the head is developed properly.[6]

Overexpression or overabundance of Cerberus is associated with the development of ectopic heads. These additional head-like structures may contain varying characteristics of a normal head (eye or eyes, brain, notochord) depending on the ratio of overabundant Cerberus to other proteins associated with anterior development that Cerberus inhibits (Wnt, Nodal, and BMP). If only Nodal is blocked, a single head will still form but with abnormalities such as cyclopia. If both Nodal and BMP or Wnt and BMP are sufficiently inhibited, ectopic, abnormal head-like structures will form. Inhibition of all three proteins by Cerberus is required for the development of complete, ectopic heads.[3]

References[edit]

  1. ^ a b "Entrez Gene: CER1". 
  2. ^ Lah M, Brodnicki T, Maccarone P, Nash A, Stanley E, Harvey RP (February 1999). "Human cerberus related gene CER1 maps to chromosome 9". Genomics 55 (3): 364–6. doi:10.1006/geno.1998.5671. PMID 10049596. 
  3. ^ a b Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis EM (1999). "The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals". Nature 397 (6721): 707–10. doi:10.1038/17820. PMC 2323273. PMID 10067895. 
  4. ^ Bouwmeester T, Kim S, Sasai Y, Lu B, De Robertis EM (1996). "Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer". Nature 382 (6592): 595–601. doi:10.1038/382595a0. PMID 8757128. 
  5. ^ Katoh M, Katoh M (2006). "CER1 is a common target of WNT and NODAL signaling pathways in human embryonic stem cells". Int. J. Mol. Med. 17 (5): 795–9. PMID 16596263. 
  6. ^ Silva AC, Filipe M, Kuerner KM, Steinbeisser H, Belo JA (2003). "Endogenous Cerberus activity is required for anterior head specification in Xenopus". Development 130 (20): 4943–53. doi:10.1242/dev.00705. PMID 12952900. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.