RASSF1

This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

Ras Association Domain Family Member 1

Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage.

Biological Process cell cycleIEA:UniProtKB-KW
Biological Process cellular response to DNA damage stimulusIMP:UniProtKB
Biological Process positive regulation of protein ubiquitinationIDA:UniProtKB
Biological Process protein stabilizationIDA:UniProtKB
Biological Process Ras protein signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cell cycleIDA:UniProtKB
Biological Process regulation of cell cycle G1/S phase transitionIMP:UniProtKB
Biological Process regulation of microtubule cytoskeleton organizationIEA:InterPro
Biological Process signal transductionManual Assertion Based On ExperimentIBA:GO_Central

Isoform A
Cytoplasm, cytoskeleton
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Cytoplasm, cytoskeleton, spindle
Cytoplasm, cytoskeleton, spindle pole
Nucleus
Localizes to cytoplasmic microtubules during interphase, to bipolar centrosomes associated with microtubules during prophase, to spindle fibers and spindle poles at metaphase and anaphase, to the midzone during early telophase, and to the midbody in late telophase in cells. Colocalizes with MDM2 in the nucleus.
Isoform C
Nucleus
Predominantly nuclear.