S100 proteiiniperhe . Esimerkkinä S100B (21q3)

 

Review

. 2015 Feb;15(2):96-109.

doi: 10.1038/nrc3893.

S100 proteins in cancer

Anne R Bresnick  ¹ , David J Weber  ² , Danna B Zimmer  ²

Affiliations

• PMID: 25614008
• PMCID: PMC4369764
• DOI: 10.1038/nrc3893

 

Tiivistelmää: Ihmisessä esiintyy S100-proteiiniperhe, jossa on 21 jäsentä. POerheenjäsenissä vallitsee korkea-asteisesti rakenteellista samankaltaisuutta, mutta toiminnallisesti niistä mikään ei voi korvata toistansa. Tämän perheen proteiinit moduloivat soluvasteita toimimalla sekä solunsisäisinä kalsiumjonin Ca(2+)sensoreina että solunulkoisina tekijöinä.

• Free PMC article
•  Abstract In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca(2+) sensors and as extracellular factors. 

Ihmisten syövissä on yleispiirteenä S100-perheenjäsenten ilmentymän säätöhäiriöt, mistä johtuen kaiken tyyppisillä syövillä osoittautuu olevan ainutlaatuinen S100 proteiinieprofiilinsa  tai tunnuksensa.

• Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature.

Koeputkitutkimuksista saatu lisääntyvä näyttö viittaa useimpien S100 proteiinin biologian olevan monimutkainen ja monitekijöinen ja näiden proteiinien osallistuvan  aktiivisti tuumoreita muodostaviin prosesseihin kuten solun prolioferaatioon, metastaasiin, angiogeneesiin ja immuunivasteen välttöön.

• Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion.

Lääkeaineiten löytymiseen tähtäävissä  ponnisteluissa on tunnistettu keinoja estää useita S100 prpoteiiniperheen jäseniä; kaksi tunnistetuista estäjistä on edennyt jo kliinisiin kokeisiin syöpäpotilaissa.

 Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. 

 Tässä katsauksessa valotetaan uusia löytöjä S100 proteiiniperheenjäsenten osasta syövän diagnostiikassa ja hoidossa, niiden  osuudesta S100  tuumoribiologian signaloinnissa  ja   S100 estäjien löytämisistä ja syöpähoitoon kehittelystä.

• This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.

PubMed Disclaimer

S100 geenit  https://pubmed.ncbi.nlm.nih.gov/22834835/

 

Esimerkki: S100 B

NCBI Gene Summary for S100B Gene

• The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3. This protein may function in Neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes. [provided by RefSeq, Jul 2008]

GeneCards Summary for S100B Gene

S100B (S100 Calcium Binding Protein B) is a Protein Coding gene. Diseases associated with S100B include Syringoma and Neurofibroma. Among its related pathways are MyD88 dependent cascade initiated on endosome and Interleukin-1 family signaling. Gene Ontology (GO) annotations related to this gene include calcium ion binding and identical protein binding. An important paralog of this gene is S100A1.

Molecular function for S100B Gene according to UniProtKB/Swiss-Prot

Function:

• Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:6487634, 20950652).
  Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer (PubMed:6487634, 20950652).
  Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites (By similarity).
  Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation (By similarity).
  Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue (By similarity).
  Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase (By similarity).
  Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity).
  Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (PubMed:20351179).
  May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity (PubMed:22399290). S100B_HUMAN,P04271