Gene regulation by SMAR1: Role in cellular homeostasis and cancer.
Changes in the composition of nuclear matrix associated proteins contribute to alterations in nuclear structure, one of the major phenotypes of malignant cancer cells. The malignancy-induced changes in this structure lead to alterations in chromatin folding, the fidelity of genome replication and gene expression programs. The nuclear matrix forms a scaffold upon which the chromatin is organized into periodic loop domains called matrix attachment regions (MAR) by binding to various MAR binding proteins (MARBPs). Aberrant expression of MARBPs modulates the chromatin organization and disrupt transcriptional network that leads to oncogenesis. Dysregulation of nuclear matrix associated MARBPs has been reported in different types of cancers. Some of these proteins have tumor specific expression and are therefore considered as promising diagnostic or prognostic markers in few cancers. SMAR1 (scaffold/matrix attachment region binding protein 1), is one such nuclear matrix associated protein whose expression is drastically reduced in higher grades of breast cancer. SMAR1 gene is located on human chromosome 16q24.3 locus, the loss of heterozygosity (LOH) of which has been reported in several types of cancers. This review elaborates on the multiple roles of nuclear matrix associated protein SMAR1 in regulating various cellular target genes involved in cell growth, apoptosis and tumorigenesis.
Malonia
Sunil Kumar
SK
National Centre for Cell Science, Pune 411007, India.
Sinha
Surajit
S
Lakshminarasimhan
Pavithra
P
Singh
Kamini
K
Jalota-Badhwar
Archana
A
Rampalli
Shravanti
S
Kaul-Ghanekar
Ruchika
R
Chattopadhyay
Samit
S
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D019940:Genes, bcl-1; D006706:Homeostasis; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000209:etiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
C417914:BANP protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta