The tumor-suppressor p53 is a multifunctional protein mainly responsible for 
maintaining genomic integrity. p53 induces its tumor-suppressor activity by 
either causing cell-cycle arrest (G(1)/S or G(2)/M) or inducing cells to undergo 
apoptosis. This function of wild-type p53 as "guardian of the genome" is 
presumably achieved by forming molecular complexes with different DNA targets as 
well as by interacting with a number of cellular proteins, e.g., Mdm2, Gadd45, 
p21, 14-3-3sigma, Bax and Apaf-1. Upon activation, p53 activates p21, which in 
turn controls the cell cycle by regulating G(1) or G(2) checkpoints. Here, we 
report SMAR1 as one such p53-interacting protein that is involved in delaying 
tumor progression in vivo as well as in regulating the cell cycle. SMAR1 is a 
newly identified MARBP involved in chromatin-mediated gene regulation. The SMAR1 
gene encodes at least 2 alternatively spliced variants: SMAR1(L) (the 
full-length form) and SMAR1(S) (the shorter form). We report that expression of 
SMAR1(S), but not of SMAR1(L), mRNA was decreased in most of the human cell 
lines examined, suggesting selective silencing of SMAR1(S). Overexpression of 
SMAR1(S) in mouse melanoma cells (B16F1) and their subsequent injection in 
C57BL/6 mice delays tumor growth. Exogenous SMAR1(S) causes significant 
retardation of B16F1 cells in the G(2)/M phase of the cell cycle compared to 
SMAR1(L). SMAR1(S) activates p53-mediated reporter gene expression in mouse 
melanoma cells, breast cancer cells (MCF-7) and p53 null cells (K562), followed 
by activation of its downstream effector, p21. We further demonstrate that SMAR1 
physically interacts and colocalizes with p53. These data together suggest that 
SMAR1 is the only known MARBP that delays tumor progression via direct 
activation and interaction with tumor-suppressor p53.