title: Overexpression of p49/STRAP alters cellular cytoskeletal structure and gross anatomy in mice.
abstract: BACKGROUND
  The protein p49/STRAP (SRFBP1) is a transcription cofactor of serum response factor (SRF) which regulates cytoskeletal and muscle-specific genes.
  
  
  RESULTS
  Two conserved domains were found in the p49/STRAP protein. The SRF-binding domain was at its N-terminus and was highly conserved among mammalian species, xenopus and zebrafish. A BUD22 domain was found at its C-terminus in three sequence databases. The BUD22 domain was conserved among mammalian p49/STRAP proteins, and yeast cellular morphogenesis proteins, which is involved in ribosome biogenesis that affects growth rate and cell size. The endogenous p49/SRAP protein was localized mainly in the nucleus but also widely distributed in the cytoplasm, and was in close proximity to the actin. Transfected GFP-p49/STRAP protein co-localized with nucleolin within the nucleolus. Overexpression of p49/STRAP reduced actin content in cultured cells and resulted in smaller cell size versus control cells. Increased expression of p49/STRAP in transgenic mice resulted in newborns with malformations, which included asymmetric abdominal and thoracic cavities, and substantial changes in cardiac morphology. p49/STRAP altered the expression of certain muscle-specific genes, including that of the SRF gene, which is a key regulator of cardiac genes at the developmental, structural and maintenance level and has two SRE binding sites.
  
  
  CONCLUSIONS
  Since p49/STRAP is a co-factor of SRF, our data suggest that p49/STRAP likely regulates cell size and morphology through SRF target genes. The function of its BUD22 domain warrants further investigation. The observed increase in p49/STRAP expression during cellular aging may contribute to observed morphological changes in senescence.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Gohar
authors.initials: G
authors.lastname: Azhar
authors.forename: Steven C
authors.initials: SC
authors.lastname: Rogers
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Foster
authors.forename: Shaoke
authors.initials: S
authors.lastname: Luo
authors.affiliation: Reynolds Institute on Aging & Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 West Markham St, #748, Little Rock, AR 72205, USA. weijeanne@uams.edu.
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Wei
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D048429:Cell Size; D005786:Gene Expression Regulation; D051379:Mice / Q000033:anatomy & histology* / Q000196:embryology / Q000235:genetics; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D026362:Serum Response Factor / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D026362:Serum Response Factor; D014157:Transcription Factors; C496544:p49-STRAP protein, mouse